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Basement membranes in the kidney of the dromedary camel (Camelus dromedarius): An immunohistochemical and ultrastructural study
Abstract
Basement membranes consist of various proteins, the major ones being laminin and collagen type IV. Primary defects in these two proteins have been extensively associated with kidney pathologies. This study aimed to establish baseline information on the immunohistochemical distribution of laminin and collagen type IV, and to corelate these with the ultrastructure of basal laminae in the uriniferous tubules of the dromedary camel. Tissue samples were taken from the kidneys of eight adult female camels, and processed for immunohistochemical and ultrastructural investigations. Strong intensity of collagen type IV was observed within the basement membranes of Bowman’s capsule. The thickness of the basal lamina of the parietal layer of Bowman's capsule varied extensively depending on the region of the renal corpuscle; the thicker areas were always associated with cuboidal epithelial cells. The glomerular basement membrane revealed strong immunostaining of laminin, whereas the mesangial matrix was strongly immunoreactive to collagen type IV. Abundant amount of laminin was found in the basement membranes of proximal convoluted tubules, thin limbs of the loop of Henle, and collecting ducts. Dense immunostainings of laminin and collagen type IV were observed in the medullary regions of uriniferous tubule, in which numerous projections extended from the basal laminae into the subjacent connective tissue. Overall, the present study revealed marked variations in the distribution of the basement membrane markers laminin and collagen type IV in the uriniferous tubules of camel kidney. The results have also shown difference in the thickness of basal laminae. This variation in thickness, however, was unlikely to be influenced by the amount of laminin and collagen type
... One of these mechanisms, which is the maintenance of electrolyte and water balance during dehydration and fast rehydration, is attributed to the kidney (Jararr and Faye, 2015). For a better understanding of this renal mechanism, several investigations have been carried out on the histology of the kidney in the dromedary camel (Abdalla and Abdalla, 1979;Safer et al., 1988;Eissa et al., 2018;Eissa et al., 2019, Abdalla, 2020. However, despite these studies, several histological features of the camel kidney remain unknown. ...
Intermediate filaments belong to a large family of proteins which contribute to the formation of the cytoskeleton. The immunolocalization of cytoskeletal proteins has been used extensively in the diagnosis of various renal pathologies. The present study described the immunolocalization of the cytoskeletal proteins vimentin, desmin, smooth muscle actin, and cytokeratin 19 in the normal kidney of the dromedary camel. Kidney samples from eight adult camels were processed for histology and immunohistochemistry. The kidney was enclosed in a renal capsule composed of vimentin immunoreactive fibroblasts and smooth muscle actin immunoreactive smooth muscle cells. The smooth muscle cells in the renal capsule did not exhibit desmin immunoreactivity. Podocytes forming the visceral layer of the glomerular capsule were immunoreactive for vimentin. Immunoreactivity for vimentin and smooth muscle actin in the parietal layer of the glomerular capsule varied, with both reactive and non-reactive cells observed. Intraglomerular mesangial cells were immunoreactive for smooth muscle actin and desmin, but non-reactive to vimentin. The endothelial lining of blood vessels was vimentin immunoreactive, while smooth muscle actin and desmin were demonstrated in the smooth muscle cells of the vessels. The thin limbs of the loops of Henle in cortical nephrons displayed vimentin immunoreactivity. The proximal and distal convoluted tubules, as well as the collecting ducts were negative to vimentin, smooth muscle actin, desmin and cytokeratin 19 immunostaining. In conclusion, the present study has revealed that similarities and differences exist in the immunolocalization of cytoskeletal proteins in the camel when compared to other mammals. The presence of smooth muscle actin in the parietal cells of the glomerular capsule suggests a contractile function of these cells. The results of the study indicate that vimentin and smooth muscle actin can be used as markers for the identification of podocytes and intraglomerular mesangial cells, respectively, in the camel kidney.
The camel is a multipurpose livestock species of great economic importance due to the benefits provided by camel products (meat, milk, wool). This review provides an overview of the impact of climate change on camel production and its adaptation mechanisms. Emphasis was also given to camel contribution to greenhouse gas (GHG) pool through methane emission. As a species well known for its extreme adaptive capacity for extreme weather conditions as compared to ruminants, camels offer huge scope for protecting the socioeconomic status of poor and marginal farmers by acting as alternate livelihood security in the changing climate scenario. The most contrasting adaptive behaviour of camel over other animals during heat stress condition is to reduce their evaporative cooling mechanisms as a measure of conserving their water resource in the body. Although camel possess extreme thermo-tolerance capability, but still drought has grown as a concern in recent years, leading to shrinkage of grazing land, and the weather extremes can give rise to malnutrition and other health concerns for camel herds. Heat stress seems to have adverse impact on both milk production and milk quality in camel. Heat stress significantly increase the packed cell volume (PCV), haemoglobin (Hb), total protein, albumin, serum glucose, aspartate amino transferase (AST); alanine amino transferase (ALT), tri-iodo-thyronine (T3), and thyroxin (T4) concentration in camels. Further, climate change also increases the incidences of emerging diseases and vector-borne diseases in particular. There are links of climate change on the occurrences of camel pox, peste des petits ruminants, babesiosis, theileriosis and trypanosomosis in camel. The heat shock protein (HSP) 70 was considered to be the ideal biological marker for quantifying heat stress in camel. The camel is a unique animal and its remarkable adaptive characteristic projects it as the animal for future as the world is preparing itself to face the untoward challenges of climate change. Hence considerable research efforts are needed to promote development of this neglected species in the changing climate scenario
This study was carried out to identify some of the obstacles to camel production in the desert of North Kordofan state. The study also exhorts the authorities to strive and struggle to solve these obstacles. An interview was made with 117 camels' owners in three areas of the state depending on the number of herds in each area (Elobeid =29, Hajiz=15, Mazroub=74). The answers were recorded onto a questionnaire consisting of 10 simple close ended questions to be answered with yes or no. The questionnaire was filled correctly (recovery rate 100%). The results of this study showed that the camels' breeding in the desert of North Kordofan is hampered with many emerging and increasing obstacles. The most serious obstacles are scarcity of pasture, water, veterinary service and ignorance. These obstacles vary significantly (p<0.05) from place to place. In conclusion the camels' herders in north Kordofan complain of serious obstacles that might lead to the demise of their herds and threat them with displacement in future. The local and central authorities should pay attention to the gravity and seriousness of ignorance of the nomads and their herds.
This study took place in Isiolo County of semi-arid northern Kenya among Borana pastoralists. Current scientific evidence indicates that climate variability is threatening reliance on cattle. This study aimed to understand whether the Borana community would let go their cattle culture and embrace camel production. The results showed that the Borana have changed their preference from cattle to camel rearing. Constraints identified as affecting camel production included the following: diseases, raiding and competition from other livestock. There is need to employ animal health workers to bail out the pastoralists from threats of livestock diseases, and to promote peace in the region.
The main objective of this study was to assess glomerular filtration rate (GFR) in the camels (Camelus dromedarius) under free water access and dehydration conditions (after a 34 days-period of water deprivation) using plasma exogenous creatinine clearance without urine collection. Trials were carried out on six nonpregnant, non-lactating and healthy female camels. Creatinine was administered as an IV bolus at a dose of 16 mg/kg body weight. Blood samples were collected at predetermined times over 24 h post-injection. Plasma creatinine concentration was analysed using Jaffé method. Creatinine clearance was calculated by pharmacokinetic analysis using a non-compartmental approach. Water deprivation induced a significant 15%- decrease in body weight but did not affect haematocrit and total plasma proteins. Mean corpuscular volume increased and red blood cells number decreased in dehydrated conditions. Dehydration produced a significant 30%-increase in plasma creatinine and mean residence time and a significant 20%-decrease in GFR. In conclusion, water deprivation decreased glomerular filtration and plasma exogenous creatinine clearance test could be used as a practical method for GFR assessment in dromedary camel in field conditions.
Basement membranes form an anatomic barrier that contains connective tissue. They are composed of type IV collagen, laminin and proteoglycans. Anti-basement membrane antibodies bind to the non-collagen site of the α3 chain of type IV collagen. A group of renal diseases, pulmonary diseases and perhaps others affecting different organs have long been associated with the presence of antibodies directed against glomerular basement membrane (GBM), alveolar basement membrane and tubular basement membrane. Goodpasture disease has a frequency of 0.5 to 1 case by million/year, and is responsible for up to 20% of crescentic glomerulonephritis in renal biopsy. It has been associated with genetic and immune abnormalities and there are usually environmental triggers preceding clinical onset. Renal disease can occur isolated or in association with pulmonary hemorrhage. In general, renal disease has a rapid progression that determines severe compromise, with rare spontaneous resolution. The diagnosis of Goodpasture disease requires the presence of the anti-GBM antibody, either in circulation or in renal tissue. The prognosis of non-treated patients is poor. The standard of care is plasma exchange combined with prednisone and cyclophosphamide. Anti-GBM antibody levels must be monitored frequently until their disappearance, and then every 6 months to confirm sustained remission in the absence of clinical signs of recurrence. Prognosis of the disease is strongly associated with its initial presentation. Survival rates are related to the degree of renal compromise at onset of the disease. Recurrence of the disease post-transplantation is low.
The dromedary camel (Camelus dromedarius) is well known for is its ability to survive harsh desert conditions. Is this survival ability due to its heat tolerance or its ability to withstand the effects of dehydration? Or are other adaptive strategies employed to overcome the harsh conditions? It is unlikely that any single factor can be attributed to the camels' tolerance to harsh environmental conditions.
Interstitial fibrosis is the common endpoint of end-stage chronic kidney disease (CKD) leading to kidney failure. The clinical course of many renal diseases, and thereby of CKD, is highly variable. One of the major challenges in deciding which treatment approach is best suited for a patient but also in the development of new treatments is the lack of markers able to identify and stratify patients with stable versus progressive disease. At the moment renal biopsy is the only means of diagnosing renal interstitial fibrosis. Novel biomarkers should improve diagnosis of a disease, estimate its prognosis and assess the response to treatment, all in a non-invasive manner. Existing markers of CKD do not fully and specifically address these requirements and in particular do not specifically reflect renal fibrosis. The aim of this review is to give an insight of the involvement of the extracellular matrix (ECM) proteins in kidney diseases and as a source of potential novel biomarkers of renal fibrosis. In particular the use of the protein fingerprint technology, that identifies neo-epitopes of ECM proteins generated by proteolytic cleavage by proteases or other post-translational modifications, might identify such novel biomarkers of renal fibrosis.
The human kidneys produce approximately 160-170 L of ultrafiltrate per day. The proximal tubule contributes to fluid, electrolyte, and nutrient homeostasis by reabsorbing approximately 60%-70% of the water and NaCl, a greater proportion of the NaHCO3, and nearly all of the nutrients in the ultrafiltrate. The proximal tubule is also the site of active solute secretion, hormone production, and many of the metabolic functions of the kidney. This review discusses the transport of NaCl, NaHCO3, glucose, amino acids, and two clinically important anions, citrate and phosphate. NaCl and the accompanying water are reabsorbed in an isotonic fashion. The energy that drives this process is generated largely by the basolateral Na(+)/K(+)-ATPase, which creates an inward negative membrane potential and Na(+)-gradient. Various Na(+)-dependent countertransporters and cotransporters use the energy of this gradient to promote the uptake of HCO3(-) and various solutes, respectively. A Na(+)-dependent cotransporter mediates the movement of HCO3(-) across the basolateral membrane, whereas various Na(+)-independent passive transporters accomplish the export of various other solutes. To illustrate its homeostatic feat, the proximal tubule alters its metabolism and transport properties in response to metabolic acidosis. The uptake and catabolism of glutamine and citrate are increased during acidosis, whereas the recovery of phosphate from the ultrafiltrate is decreased. The increased catabolism of glutamine results in increased ammoniagenesis and gluconeogenesis. Excretion of the resulting ammonium ions facilitates the excretion of acid, whereas the combined pathways accomplish the net production of HCO3(-) ions that are added to the plasma to partially restore acid-base balance.
Basement membranes are specialized extracellular matrices consisting of tissue-specific organizations of multiple matrix molecules and serve as structural barriers as well as substrates for cellular interactions. The network of collagen IV is thought to define the scaffold integrating other components such as, laminins, nidogens or perlecan, into highly organized supramolecular architectures. To analyze the functional roles of the major collagen IV isoform alpha1(IV)(2)alpha2(IV) for basement membrane assembly and embryonic development, we generated a null allele of the Col4a1/2 locus in mice, thereby ablating both alpha-chains. Unexpectedly, embryos developed up to E9.5 at the expected Mendelian ratio and showed a variable degree of growth retardation. Basement membrane proteins were deposited and assembled at expected sites in mutant embryos, indicating that this isoform is dispensable for matrix deposition and assembly during early development. However, lethality occurred between E10.5-E11.5, because of structural deficiencies in the basement membranes and finally by failure of the integrity of Reichert's membrane. These data demonstrate for the first time that collagen IV is fundamental for the maintenance of integrity and function of basement membranes under conditions of increasing mechanical demands, but dispensable for deposition and initial assembly of components. Taken together with other basement membrane protein knockouts, these data suggest that laminin is sufficient for basement membrane-like matrices during early development, but at later stages the specific composition of components including collagen IV defines integrity, stability and functionality.
Congenital nephrotic syndrome (CNS) is clinically and genetically heterogeneous, with mutations in WT1, NPHS1 and NPHS2 accounting for part of cases. We recently delineated a new autosomal recessive entity comprising CNS with diffuse mesangial sclerosis and distinct ocular anomalies with microcoria as the leading clinical feature (Pierson syndrome). On the basis of homozygosity mapping to markers on chromosome 3p14-p22, we identified homozygous or compound heterozygous mutations of LAMB2 in patients from five unrelated families. Most disease-associated alleles were truncating mutations. Using immunohistochemistry and western blotting we could demonstrate that the respective LAMB2 mutations lead to loss of laminin beta2 expression in kidney and other tissues studied. Laminin beta2 is known to be abundantly expressed in the glomerular basement membrane (GBM) where it is thought to play a key role in anchoring as well as differentiation of podocyte foot processes. Lamb2 knockout mice were reported to exhibit congenital nephrosis in association with anomalies of retina and neuromuscular junctions. By studying ocular laminin beta2 expression in unaffected controls, we detected the strongest expression in the intraocular muscles corresponding well to the characteristic hypoplasia of ciliary and pupillary muscles observed in patients. Moreover, we present first clinical evidence of severe impairment of vision and neurodevelopment due to LAMB2 defects. Our current data suggest that human laminin beta2 deficiency is consistently and specifically associated with this particular oculorenal syndrome. In addition, components of the molecular interface between GBM and podocyte foot processes come in the focus as potential candidates for isolated and syndromic CNS.
Juvenile onset renal disease is described in 2 male and 2 female young Rottweiler dogs. Histologic changes in all dogs were cystic dilatation of Bowman's space, mesangial hypercellularity, and glomerulosclerosis. Three dogs also had glomerular crescents and moderate to severe interstitial fibrosis. Electron microscopy revealed glomerular basement membranes of variable thickness, with extensive splitting or lamellation of the lamina densa. These ultrastructural findings are similar to those found in people and in other breeds of dogs with inherited defects in type IV collagen.
Cambridge Core - Pathology and Laboratory Science - Silva's Diagnostic Renal Pathology - edited by Xin Jin (Joseph) Zhou
The renal medulla produces concentrated urine through the generation of an osmotic gradient that progressively increases from the cortico-medullary boundary to the inner medullary tip. In the outer medulla, the osmolality gradient arises principally from vigorous active transport of NaCl, without accompanying water, from the thick ascending limbs of short- and longlooped nephrons. In the inner medulla, the source of the osmotic gradient has not been identified. Recently, there have been important advances in our understanding of key components of the urine-concentrating mechanism, including (a) better understanding of the regulation of water, urea, and sodium transport proteins; (b) better resolution of the anatomical relationships in the medulla; and (c) improvements in mathematical modeling of the urine-concentrating mechanism. Continued experimental investigation of signaling pathways regulating transepithelial transport, both in normal animals and in knockout mice, and incorporation of the resulting information into mathematical simulations may help to more fully elucidate the mechanism for concentrating urine in the inner medulla. Expected final online publication date for the Annual Review of Physiology Volume 76 is February 10, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
The ability of mammals to produce urine hyperosmotic to plasma requires the generation of a gradient of increasing osmolality along the medulla from the corticomedullary junction to the papilla tip. Countercurrent multiplication apparently establishes this gradient in the outer medulla, where there is substantial transepithelial reabsorption of NaCl from the water-impermeable thick ascending limbs of the loops of Henle. However, this process does not establish the much steeper osmotic gradient in the inner medulla, where there are no thick ascending limbs of the loops of Henle and the water-impermeable ascending thin limbs lack active transepithelial transport of NaCl or any other solute. The mechanism generating the osmotic gradient in the inner medulla remains an unsolved mystery, although it is generally considered to involve countercurrent flows in the tubules and vessels. A possible role for the three-dimensional interactions between these inner medullary tubules and vessels in the concentrating process is suggested by creation of physiologic models that depict the three-dimensional relationships of tubules and vessels and their solute and water permeabilities in rat kidneys and by creation of mathematical models based on biologic phenomena. The current mathematical model, which incorporates experimentally determined or estimated solute and water flows through clearly defined tubular and interstitial compartments, predicts a urine osmolality in good agreement with that observed in moderately antidiuretic rats. The current model provides substantially better predictions than previous models; however, the current model still fails to predict urine osmolalities of maximally concentrating rats.
This study describes the distribution of vimentin, desmin, smooth muscle actin (SMA) and laminin in the oviduct of the immature and mature Japanese quail. The cytoskeletal proteins vimentin, desmin and SMA have been shown to be involved in cellular support, differentiation, migration and contractility. Laminin is a major component of basement membranes. Luminal epithelia in the infundibular and magnal regions of immature and mature birds exhibited strong vimentin immunoreactivity. Luminal epithelial cells exhibiting strong vimentin immunoreactivity were present in the isthmus and shell gland regions of only mature quails. Infundibular glandular grooves displayed strong vimentin immunostaining. In contrast, the glandular epithelia of the magnum, isthmus and shell gland were vimentin immunonegative. Fibroblasts and vascular endothelial cells in the lamina propria of the oviductal regions studied exhibited strong vimentin immunostaining. Smooth muscle cells forming the tunica muscularis and vascular tunica media displayed strong desmin and SMA immunostaining. Strong laminin immunostaining was demonstrated in the basement membranes associated with smooth muscle cells, as well as in the basement membranes underlying the luminal and glandular epithelia. In conclusion, this study has shown that the immunolocalization of desmin, SMA and laminin in the oviduct of the Japanese quail is similar to that in the domestic fowl. However, differences in the immunoexpression of vimentin in the LE of the two avian species were shown to exist. In addition, the study has shown that the immunolocalization of vimentin in the Japanese quail varies depending on the oviductal region, as well as the developmental stage of the oviduct.
The thin limbs of the loop of Henle, which comprise the intermediate segment, connect the proximal tubule to the distal tubule and lie entirely within the renal medulla. The descending thin limb consists of at least two or three morphologically and functionally distinct subsegments and participates in transepithelial transport of NaCl, urea, and water. Only one functionally distinct segment is recognized for the ascending thin limb, which carries out transepithelial transport of NaCl and urea in the reabsorptive and/or secretory directions. Membrane transporters involved with passive transcellular Cl, urea, and water fluxes have been characterized for thin limbs; however, these pathways do not account for all transepithelial fluid and solute fluxes that have been measured in vivo. The paracellular pathway has been proposed to play an important role in transepithelial Na and urea fluxes in defined thin-limb subsegments. As the transport pathways become clearer, the overall function of the thin limbs is becoming better understood. Primary and secondary signaling pathways and protein-protein interactions are increasingly recognized as important modulators of thin-limb cell function and cell metabolism. These functions must be investigated under diverse extracellular conditions, particularly for those cells of the deep inner medulla that function in an environment of wide variation in hyperosmolality. Transgenic mouse models of several key water and solute transport proteins have provided significant insights into thin-limb function. An understanding of the overall architecture of the medulla, including juxtapositions of thin limbs with collecting ducts, thick ascending limbs, and vasa recta, is essential for understanding the role of the kidney in maintaining Na and water homeostasis, and for understanding the urine concentrating mechanism. © 2012 American Physiological Society. Compr Physiol 2:2063-2086, 2012.
The aim of this study is to compare the accuracy and clinical use of light and transmission electron microscopy in detecting the early stages of renal pathologies in domestic animals. We examined 30 samples of renal tissue from cats and dogs referred to the Veterinary Hospital of the Department of Animal Pathology for different systemic diseases. The progressions of the kidney pathologies were classified using the scheme system proposed by the International Renal Interest Society. All samples were submitted for conventional histology and ultrastructural examination. Our study shows that electron microscopy is necessary to complete the histological examinations, especially to define early stages of kidney diseases (minimal changes disease, epithelial tubular pathologies, tubular basement membrane and glomerular basement membrane changes). Electron microscopy can be more accurate in defining the level of focal lesion, and permits discrimination between different clinical and pathological alterations such as fibrillary deposits. In conclusion, transmission electron microscopy associated with clinical, histological, histochemical and immunological examinations, is an essential method for diagnosis and prognosis of renal disease.
The nephron of the one-humped camel Camelus dromedarius was investigated by light and transmission electron microscopy. Besides the many features common to other mammalian kidneys, the nephron of the camel is unique in having an unusually thick basal lamina underlying the epithelial cells of the nephron, the thickest being found in part of the parietal layer of Bowman's capsule and the thin limb of the loop of Henle. In the latter, the membrane usually appears lamellated and contains numerous tiny vesicles. In other parts of the nephron, the basal lamina usually has a homogenous appearance. The possible significance of the thickening of the basal lamina is discussed in relation to the general high renal efficiency of the camel.
Mesangial cells are smooth muscle-like pericytes that abut and surround the filtration capillaries within the glomerulus. Studies of the fine ultrastructure of the glomerulus show that the mesangial cell and the capillary basement membrane form a biomechanical unit capable of regulating filtration surface area as well as intraglomerular blood volume. Structural and functional studies suggest that mesangial cells regulate filtration rate in both a static and dynamic fashion. Mesangial excitability enables a homeostatic intraglomerular stretch reflex that integrates an increase in filtration pressure with a reduction in capillary surface area. In addition, mesangial tone is regulated by diverse vasoactive hormones. Agonists, such as angiotensin II, contract mesangial cells through a signal transduction pathway that releases intracellular stores of Ca2+, which subsequently activate nonselective cation channels and Cl- channels to depolarize the plasma membrane. The change in membrane potential activates voltage-gated Ca2+ channels, allowing Ca2+ cell entry and further activation of depolarizing conductances. Contraction and entry of cell Ca2+ are inhibited only when Ca2+-activated K+ channels (BK(Ca)) are activated and the membrane is hyperpolarized toward the K+ equilibrium potential. The mesangial BK(Ca) is a weak regulator of contraction in unstimulated cells; however, the gain of the feedback is increased by atrial natriuretic peptide, nitric oxide, and the second messenger cGMP, which activates protein kinase G and decreases both the voltage and Ca2+ activation thresholds of BK(Ca) independent of sensitivity. This enables BK(Ca) to more effectively counter membrane depolarization and voltage-gated Ca2+ influx. After hyperpolarizing the membrane, BK(Ca) rapidly inactivates because of dephosphorylation by protein phosphatase 2A. Regulation of ion channels has been linked casually to hyperfiltration during early stages of diabetes mellitus. Determining the signaling pathways controlling the electrophysiology of glomerular mesangial cells is important for understanding how glomerular filtration rate is regulated in health and disease.
Renal basement membrane components. Basement membranes are specialized extracellular matrices found throughout the body. They surround all epithelia, endothelia, peripheral nerves, muscle cells, and fat cells. They play particularly important roles in the kidney, as demonstrated by the fact that defects in renal basement membranes are associated with kidney malfunction. The major components of all basement membranes are laminin, collagen IV, entactin/nidogen, and sulfated proteoglycans. Each of these describes a family of related proteins that assemble with each other in the extracellular space to form the basement membrane. Over the last few years, new basement membrane components that are expressed in the kidney have been discovered. Here, the major components and their localization in mature and developing renal basement membranes are described. In addition, the phenotypes of basement membrane component gene mutations, both naturally occurring and experimental, are discussed, as is the aberrant deposition of basement membrane proteins in the extracellular matrix in several renal diseases.
Laminins are alpha-beta-gamma heterotrimeric components of all basement membranes. Laminins are now known to play the central role in organizing and establishing the basement membrane. The diversity of laminins allows them to impart special structural and signaling properties to the basement membrane. Of the 12 known laminin chain genes, 10 have been either found to be mutated in humans or experimentally mutated in mice. This has led to great progress over the last several years towards understanding both the functions of laminins and the reasons for their great diversity. In this review, I will summarize the in vivo studies in mice and humans that have contributed to this new knowledge.
Four decades have passed since the first discovery of collagen IV by Kefalides in 1966. Since then collagen IV has been investigated extensively by a large number of research laboratories around the world. Advances in molecular genetics have resulted in identification of six evolutionary related mammalian genes encoding six different polypeptide chains of collagen IV. The genes are differentially expressed during the embryonic development, providing different tissues with specific collagen IV networks each having unique biochemical properties. Newly translated alpha-chains interact and assemble in the endoplasmic reticulum in a chain-specific fashion and form unique heterotrimers. Unlike most collagens, type IV collagen is an exclusive member of the basement membranes and through a complex inter- and intramolecular interactions form supramolecular networks that influence cell adhesion, migration, and differentiation. Collagen IV is directly involved in a number of genetic and acquired disease such as Alport's and Goodpasture's syndromes. Recent discoveries have also highlighted a new and direct role for collagen IV in the development of rare genetic diseases such as cerebral hemorrhage and porencephaly in infants and hemorrhagic stroke in adults. Years of intensive investigations have resulted in a vast body of information about the structure, function, and biology of collagen IV. In this review article, we will summarize essential findings on the structural and functional relationships of different collagen IV chains and their roles in health and disease.
Junqueira's Basic Histology: Text and Atlas, twelfth ed. McGraw-Hill Camoanies
- A L Mescher
Mescher, A.L., 2010. Junqueira's Basic Histology: Text and Atlas, twelfth ed.
McGraw-Hill Camoanies, New York; London.
- L Eissa
L. Eissa, et al.
Acta Histochemica 121 (2019) 419-429