Lene Niemann Nejsum- PhD Dr. Med.
- Professor (Full) at Aarhus University
Lene Niemann Nejsum
- PhD Dr. Med.
- Professor (Full) at Aarhus University
About
85
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Publications (85)
Cellular changes in carcinomas include alterations in cell proliferation, cell migration, cell-cell adhesion and cellular polarity. In vitro studies have revealed that the water channels, aquaporin-1 (AQP1) and AQP3 can influence cell migration and cell-cell adhesion. Of note, we previously showed that AQP1 overexpression reduced levels of cell-cel...
Antibody‐based CD47 blockade aims to activate macrophage phagocytosis of tumor cells. However, macrophages possess a high degree of phenotype heterogeneity that likely influences phagocytic capacity. In murine models, proinflammatory (M1) activation increases macrophage phagocytosis of tumor cells, but in human models, results have been conflicting...
Acute pyelonephritis (APN) is most frequently caused by uropathogenic Escherichia coli (UPEC), which ascends from the bladder to the kidneys during a urinary tract infection. Patients with APN have been reported to have reduced renal concentration capacity under challenged conditions, polyuria and increased aquaporin-2 (AQP2) excretion in the urine...
Chronic kidney disease (CKD) represents a major public health burden with increasing prevalence. Current therapies focus on delaying CKD progression, underscoring the need for innovative treatments. This necessitates animal models that accurately reflect human kidney pathologies, particularly for studying potential reversibility and regenerative me...
The shuttling of renal collecting duct aquaporin-2 (AQP2) between intracellular vesicles and the apical plasma membrane is paramount for regulation of renal water reabsorption. The binding of the circulating antidiuretic hormone arginine vasopressin (AVP), to the basolateral AVP receptor increases intracellular cAMP, which ultimately leads to AQP2...
Alpha‐synuclein (aSN) is a membrane‐associated and intrinsically disordered protein, well known for pathological aggregation in neurodegeneration. However, the physiological function of aSN is disputed. Pull‐down experiments have pointed to plasma membrane Ca ²⁺ ‐ATPase (PMCA) as a potential interaction partner. From proximity ligation assays, we f...
Aquaporins are water channels that facilitate passive water transport across cellular membranes following an osmotic gradient and are essential in the regulation of body water homeostasis. Several aquaporins are overexpressed in breast cancer, and AQP1, AQP3 and AQP5 have been linked to spread to lymph nodes and poor prognosis. The subgroup aquagly...
Aquaporin (AQP) water channels are pivotal to renal water handling and therefore in the regulation of body water homeostasis. However, beyond the kidney, AQPs facilitate water reabsorption and secretion in other cells and tissues, including sweat and salivary glands and the gastrointestinal tract. A growing body of evidence has also revealed that A...
Chronic wounds are defined as wounds that fail to proceed through the normal phases of wound healing; a complex process involving different dynamic events including migration of keratinocytes in the epidermis. Chronic wounds are estimated to affect 1-2% of the human population worldwide and are a major socioeconomic burden. The prevalence of chroni...
Animal and human tissues are used extensively in physiological and pathophysiological research. Due to both ethical considerations and low availability, it is essential to maximize the use of these tissues. Therefore, the aim was to develop a new method allowing for multiplex immunofluorescence (IF) staining of kidney sections in order to reuse the...
Sex hormones play an important role in the regulation of water homeostasis, and we have previously shown that tamoxifen (TAM), a selective estrogen receptor modulator (SERM), affects the regulation of aquaporin (AQP)-2. In this study, we investigated the effect of TAM on the expression and localization of AQP3 in collecting ducts using various anim...
Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare X‐linked disease caused by gain‐of‐function mutations of arginine vasopressin receptor 2 (V2R). Patients with NSIAD are characterized by the inability to excrete a free water load and by inappropriately increased urinary osmolality despite very low levels of plasma vasopressin, re...
Motor neuron development requires an orchestrated action of trophic factors and guidance cues for axons to reach their targets. Here, we identify SorCS2 as a novel receptor for progranulin (PGRN) that is required for motor axon outgrowth in zebrafish and mice. In both species motor neurons express SorCS2, and PGRN is produced in cells juxta-positio...
Breast carcinomas originate from cells in the terminal duct-lobular unit. Carcinomas are associated with increased cell proliferation and migration, altered cellular adhesion, as well as loss of epithelial polarity. In breast cancer, aberrant and high levels of AQP5 are associated with increased metastasis, poor prognosis and cancer recurrence. AQP...
Aquaporin (AQP) water channels facilitate water transport across cellular membranes and are essential in regulation of body water balance. Moreover, several AQPs are overexpressed or ectopically expressed in breast cancer. Interestingly, several in vitro studies have suggested that AQPs can affect the response to conventional anticancer chemotherap...
The water channel aquaporin‐5 (AQP5) is essential in transepithelial water transport in secretory glands. AQP5 is ectopically overexpressed in breast cancer where expression is associated with lymph node metastasis and poor prognosis. Besides the role in water transport, AQP5 has been found to play a role in cancer metastasis, migration, and prolif...
Aim
Renal fibrosis is a major driver of chronic kidney disease, yet current treatment strategies are ineffective in attenuating fibrogenesis. The cyclooxygenase/prostaglandin system plays a key role in renal injury and holds great promise as a therapeutic target. Here, we used a translational approach to evaluate the role of the PGE2-EP1 receptor i...
Aim
Aquaporin-2 (AQP2) shuttling between intracellular vesicles and the apical plasma membrane is pivotal in arginine vasopressin-mediated urine concentration and is dysregulated in multiple diseases associated with water balance disorders. Children and adults with acute pyelonephritis have a urinary concentration defect and studies in children rev...
The canonical function of aquaporin (AQP) water channels is to facilitate passive transport of water across cellular membranes making them essential in regulation of body water homeostasis. Moreover, AQPs, including AQP1, have been found to be overexpressed in multiple cancer types, including breast cancer, where AQP1 overexpression is associated w...
Aquaporins are water channel proteins facilitating passive transport of water across cellular membranes. Aquaporins are over‐ or ectopically expressed in a multitude of cancers, including pancreatic ductal adenocarcinoma, which is a highly aggressive cancer with low survival rate. Evidence suggests that aquaporins can affect multiple cellular proce...
Regulated vesicle exocytosis is a key response to extracellular stimuli in diverse physiological processes; including hormone regulated short-term urine concentration. In the renal collecting duct, the water channel aquaporin-2 localizes to the apical plasma membrane as well as small, sub-apical vesicles. In response to stimulation with the antidiu...
Introduction:
Vaginal colonization with Streptococcus agalactiae (group B streptococci) is hypothesized to constitute a risk factor for Preterm Prelabor Rupture of Membranes. In vitro studies have shown that S. agalactiae strains isolated from infants with neonatal sepsis adhere to chorion cells of the human chorioamniotic membrane. However, it is...
Aquaporin (AQP) water channels facilitate passive transport of water across cellular membranes following an osmotic gradient. AQPs are expressed in a multitude of epithelia, endothelia, and other cell types where they play important roles in physiology, especially in the regulation of body water homeostasis, skin hydration, and fat metabolism. AQP...
Aquaporins (AQPs) are water channels that facilitate transport of water across cellular membranes. AQPs are overexpressed in several cancers. Especially in breast cancer, AQP5 overexpression correlates with spread to lymph nodes and poor prognosis. Previously, we showed that AQP5 expression reduced cell-cell adhesion by reducing levels of adherens...
The presence of extracellular vesicles (EVs) in milk has gained interest due to their capacity to modulate the infant’s intestinal and immune system. Studies suggest that milk EVs are enriched in immune-modulating proteins and miRNA, highlighting their possible health benefits to infants. To assess uptake of milk EVs by intestinal epithelial cells,...
Herein, we characterize the cellular uptake of a DNA structure generated by rolling circle DNA amplification. The structure, termed nanoflower, was fluorescently labeled by incorporation of ATTO488-dUTP allowing the intracellular localization to be followed. The nanoflower had a hydrodynamic diameter of approximately 300 nanometer and was non-toxic...
Phenomycin is a bacterial mini-protein of 89 amino acids discovered more than 50 years ago with toxicity in the nanomolar regime toward mammalian cells. The protein inhibits the function of the eukaryotic ribosome in cell-free systems and appears to target translation initiation. Several fundamental questions concerning the cellular activity of phe...
It is almost 40 years since Barry Marshal and Robin Warrens identified and recovered Helicobacter pylori (H. pylori) from gastric biopsy specimens. They later demonstrated the role of H. pylori in peptic ulcers and in 2005, they were awarded the Nobel Prize in medicine for these groundbreaking discoveries. Later, it became clear that H. pylori has...
Aquaporin‐5 (AQP5) plays a role in breast cancer cell migration. This study aimed to identify AQP5‐targeting miRNAs and examine their effects on breast cancer cell migration through exosome‐mediated delivery. Bioinformatic analyses identified miR‐1226‐3p, miR‐19a‐3p, and miR‐19b‐3p as putative regulators of AQP5 mRNA. Immunoblotting revealed a decr...
The importance of the IFN-induced oligoadenylate synthetase (OAS) proteins and the OAS/RNase L pathway in the innate response against viral pathogens is well-established, however the observed differences in anti-viral activity between the human OAS1 p46 and p42 isoforms are not fully understood. The protein expression of these isoforms is determine...
Phenomycin is a bacterial mini-protein of 89 amino acids discovered more than 50 years ago with toxicity in the nanomolar regime towards mammalian cells. The protein inhibits the function of the eukaryotic ribosome in cell free systems and appears to target translation initiation. Several fundamental questions concerning the cellular activity of ph...
It is well known that sepsis and inflammation reduce male fertility. Within the testis, toll-like receptor 3 (TLR3) is constitutively expressed and recognizes double-stranded RNA (dsRNA) from viruses, degraded bacteria, damaged tissues and necrotic cells. To characterize the potential role of TLR3 in response to testicular infections, its expressio...
Arginine vasopressin (AVP) mediates water reabsorption in the kidney collecting ducts through regulation of aquaporin-2 (AQP2). Also, estrogen has been known to regulate AQP2. Consistently, we previously demonstrated that tamoxifen (TAM), a selective estrogen receptor modulator, attenuates the downregulation of AQP2 in lithium-induced nephrogenic d...
AQP2 fine-tunes urine concentration in response to the antidiuretic hormone vasopressin. In addition, AQP2 has been suggested to promote cell migration and epithelial morphogenesis. A cell system allowing temporal and quantitative control of expression levels of AQP2 and phospho-mimicking mutants has been missing, so has a system allowing expressio...
Plasticity of epithelial cell‐cell adhesion is vital in epithelial homeostasis and is regulated in multiple processes associated with cell migration, such as embryogenesis and wound healing. In cancer, cell‐cell adhesion is compromised and is associated with increased cell migration and metastasis. Aquaporin (AQP) water channels facilitate water tr...
Several aquaporins (AQP) water channels are short-term regulated by the messenger cyclic adenosine monophosphate (cAMP), including AQP3. Bulk measurements show that cAMP can change diffusive properties of AQP3, however, it remains unknown how elevated cAMP affects AQP3 organization at the nanoscale. Here we analyzed AQP3 nano-organization following...
Key points
Exogenous Na⁺/H⁺ exchanger 1 (NHE1) expression stimulated the collective migration of epithelial cell sheets
Stimulation with epidermal growth factor, a key morphogen, primarily increased migration of the front row of cells, whereas NHE1 increased that of submarginal cell rows, and the two stimuli were additive
Accordingly, NHE1 localize...
Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent edema attacks associated with morbidity and mortality. HAE results from variations in the SERPING1 gene encoding C1 inhibitor (C1INH), a serine protease inhibitor (serpin). Reduced plasma levels of C1INH lead to enhanced activation of the contact system triggeri...
Enteropathogenic Escherichia coli (EPEC) causes watery diarrhea when colonizing the surface of enterocytes. The translocated intimin receptor (Tir):intimin receptor complex facilitates tight adherence to epithelial cells and formation of actin pedestals beneath EPEC. We found that the host cell adherens junction protein E-cadherin (Ecad) was recrui...
Photoactivated localization microscopy (PALM) is an ingenious super-resolution imaging technique that produces 2D point patterns of proteins. Individual proteins may appear as small artificial clusters of points, due to multiple blinking of individual fluorophores. The proteins may also cluster together, and in such cases a pertinent model for a PA...
Negative regulation of immune pathways is essential to achieve resolution of immune responses and to avoid excess inflammation. DNA stimulates type I IFN expression through the DNA sensor cGAS, the second messenger cGAMP, and the adaptor molecule STING Here, we report that STING degradation following activation of the pathway occurs through autopha...
Aquaporin-5 (AQP5) is a plasma membrane water channel mainly expressed in secretory glands. Increased expression of AQP5 is observed in multiple cancers, including breast cancer, where high expression correlates with the degree of metastasis and poor prognosis. Moreover, studies in cancer cells have suggested that AQP5 activates Ras signaling, driv...
Increasing evidence suggests that the water/glycerol channel aquaporin-3 (AQP3) plays a pivotal role in cancer metastasis. AQP3 knockout mice were resistant to skin tumor formation and overexpression correlated with metastasis and poor prognosis in patients with breast or gastric cancer. In cultured cancer cells, increased AQP3 expression stimulate...
Quantification of intracellular bacterial colonies is useful in strategies directed against bacterial attachment, subsequent cellular invasion and intracellular proliferation. An automated, high-throughput microscopy-method was established to quantify the number and size of intracellular bacterial colonies in infected host cells (Detection and quan...
Aberrant levels of aquaporin-5 (AQP5) expression have been observed in several types of cancer, including breast cancer, where AQP5 overexpression is associated with metastasis and poor prognosis. In cultured cancer cells, AQP5 facilitates cell migration and activates Ras signaling. Both increased cell migration and Ras activation are associated wi...
Renal ischemia/reperfusion (I/R) can lead to impaired urine concentration ability and increased fractional excretion of sodium (FeNa). Local ischemic preconditioning improves renal water and sodium handling after I/R injury. Here, we investigate whether remote ischemic perconditioning (rIPeC) prevents dysregulation of renal water and salt handling...
Prolactin (PRL) and its receptor the PRLR are implicated in breast cancer invasiveness, although their exact roles remain controversial. The Na(+)/H(+) exchanger NHE1 plays essential roles in cancer cell motility and invasiveness, but the PRLR and NHE1 have not previously been linked. Here, we show that in T47D human breast cancer cells, which expr...
Background
Autosomal dominant inheritance of congenital nephrogenic diabetes insipidus (CNDI) is rare and usually caused by variations in the AQP2 gene. We have investigated the genetic and molecular background underlying symptoms of diabetes insipidus (DI) in a Swedish family with autosomal dominant inheritance of the condition.
Methods
The proba...
Enteropathogenic Escherichia coli (EPEC) is a bacterial pathogen that infects the epithelial lining of the small intestine and causes diarrhea. Upon attachment to the intestinal epithelium, EPEC uses a Type III Secretion System to inject its own high affinity receptor Translocated intimin receptor (Tir) into the host cell. Tir facilitates tight adh...
Aquaporin-5 (AQP5) facilitates passive water transport in glandular epithelia in response to secretory stimuli via intracellular pathways involving calcium release, cAMP and protein kinase A (PKA). In epithelial plasma membranes, AQP5 may be acutely regulated to facilitate water transport in response to physiological stimuli by changes in protein m...
Micropatterning enabled semiquantitation of basolateral proteins in lateral and basal membranes of the same cell. Lateral diffusion coefficients of basolateral aquaporin-3 (AQP3-EGFP) and EGFP-AQP4 were extracted from "lateral" and "basal" membranes using identical live-cell imaging and k-space Image Correlation Spectroscopy (kICS). To simultaneous...
Lateral diffusion and compartmentalization of plasma membrane proteins are tightly regulated in cells and thus, studying these processes will reveal new insights to plasma membrane protein function and regulation. Recently, k-Space Image Correlation Spectroscopy (kICS)(1) was developed to enable routine measurements of diffusion coefficients direct...
Regulated urine concentration takes place in the renal collecting duct upon arginine vasopressin (AVP) stimulation, where subapical vesicles containing aquaporin-2 (AQP2) are inserted into the apical membrane instantly increasing water reabsorption and urine concentration. The reabsorped water exits via basolateral AQP3 and AQP4. Upon long-term sti...
Aquaporin-3 (AQP3) and aquaporin-4 (AQP4) are homologous proteins expressed in the basolateral plasma membrane of kidney collecting duct principal cells, where they mediate the exit pathway for apically reabsorbed water. Although both proteins are localized to the same plasma membrane domain, it is unknown if they are sorted together in the Golgi,...
This paper presents the use of the Quartz Crystal Microbalance with Dissipation (QCM-D) combined with Surface Plasmon Resonance (SPR) to probe protein adsorption at nanopatterned surfaces. Three different types of adsorbing materials, representing rigid discrete nanoparticles, dense protein films and soft low density films have been studied on syst...
The patterning of biomolecules at the nanoscale provides a powerful method to investigate cellular adhesion processes. A novel method for patterning is presented that is based on colloidal monolayer templating combined with multiple and angled deposition steps. Patterns of gold and SiO(2) layers are used to generate complex protein nanopatterns ove...
Regulation of the microtubule- and actin-binding protein adenomatous polyposis coli (APC) is crucial for the formation of cell extensions in many cell types. This process requires inhibition of glycogen synthase kinase-3β (GSK-3β), which otherwise phosphorylates APC and decreases APC-mediated microtubule bundling. Although it is assumed, therefore,...
The role of ligand spatial distribution on the formation of cadherin mediated cell-cell contacts is studied utilizing nanopatterns of E-cadherin ligands. Protein patches ranging in size from 100 to 800 nm prepared by colloidal lithography critically influence adhesion, spreading, and formation of adherence junctions in epithelial cells. Cells at 10...
Mutations in the arginine vasopressin receptor 2 (AVPR2) gene can cause X-linked nephrogenic diabetes insipidus (NDI) characterized by the production of large amounts of urine and
an inability to concentrate urine in response to the antidiuretic hormone vasopressin. We have identified a novel mutation
in the AVPR2 gene (L170P) located in the fourth...
Loss of water through the immature skin can lead to hypothermia and dehydration in preterm infants. The water and glycerol channel aquaglyceroporin-3 (AQP3) is abundant in fetal epidermis and might influence epidermal water handling and transepidermal water flux around birth. To investigate the role of AQP3 in immature skin, we measured in vivo tra...
Establishment and maintenance of epithelial cell surface polarity is of vital importance for the correct function of transporting epithelia. To maintain normal cell function, the distribution of apical and basal-lateral proteins is highly regulated and defects in expression levels or plasma membrane targeting can have severe consequences. It has be...
Mechanisms involved in maintaining plasma membrane domains in fully polarized epithelial cells are known, but when and how directed protein sorting and trafficking occur to initiate cell surface polarity are not. We tested whether establishment of the basolateral membrane domain and E-cadherin-mediated epithelial cell-cell adhesion are mechanistica...
Atrial natriuretic peptide (ANP) acutely promotes water and sodium excretion, whereas subchronic effects involve water retention. Renal hemodynamics, water and sodium excretion, and aquaporin-2 (AQP2) and epithelial Na channel (ENaC) subcellular trafficking were determined in response to continuous ANP infusion in conscious rats, where body sodium...
Aquaporins are channels that facilitate movement of water across lipid bilayers. They are expressed in multiple tissues and are essential for regulation of body water homeostasis. The kidney is the main organ responsible for this regulation, and at least seven aquaporins are expressed at distinct sites in the kidney. Aquaporin expression correlates...
In isolated sweat glands, bumetanide inhibits sweat secretion. The mRNA encoding bumetanide-sensitive Na(+)-K(+)-Cl(-) cotransporter (NKCC) isoform 1 (NKCC1) has been detected in sweat glands; however, the cellular and subcellular protein localization is unknown. Na(+)/H(+) exchanger (NHE) isoform 1 (NHE1) protein has been localized to both the duc...
The present study examined the role of PKA and serine256 (S256) phosphorylation for AQP2 trafficking and recycling using cells transfected with wild-type AQP2 (AQP2-WT) or mutant AQP2 and high-resolution confocal microscopic techniques. In transiently transfected MDCK-C7 cells, stimulation with forskolin induced translocation of AQP2-WT to the plas...
The choroid plexus epithelium of the brain ventricular system produces the majority of the cerebrospinal fluid and thereby defines the ionic composition of the interstitial fluid in the brain. The transepithelial movement of Na+ and water in the choroid plexus depend on a yet-unidentified basolateral stilbene-sensitive Na+-HCO3- uptake protein. Rev...
The mocha mouse is an autosomal recessive pigment mutant on mouse chromosome 10 caused by a deletion in the gene for the delta subunit of the adaptor-like complex AP-3. Based on zinc transporter 3 (ZnT3) immunohistochemistry, zinc TSQ fluorescence and a modified Timm method, previous studies found a lack of histochemically-detectable zinc and a sub...
In the extremely preterm infant, high transepidermal water loss (TEWL) can result in severe dehydration. TEWL has been attributed to the structural properties of the epidermis but might also be influenced by mechanisms that facilitate water transport. To investigate whether aquaporins (AQP) may be involved in the extreme losses of water through imm...
Magnesium is an essential ion involved in many biochemical and physiological processes. Homeostasis of magnesium levels is tightly regulated and depends on the balance between intestinal absorption and renal excretion. However, little is known about specific proteins mediating transepithelial magnesium transport. Using a positional candidate gene a...
The distribution and function of aquaporins (AQPs) have not previously been defined in sweat glands. In this study, AQP1, AQP3, and AQP5 mRNA were demonstrated in rat paw by reverse transcription (RT)-PCR, but AQP2 and AQP4 were not. AQP1, AQP3, and AQP5 protein were confirmed in these tissues by immunoblotting. AQP1 was identified in capillary end...
The novel member of the claudin multigene family, paracellin-1/claudin-16, encoded by the gene PCLN1, is a renal tight junction protein that is involved in the paracellular transport of magnesium and calcium in the thick ascending limb of Henle's loop. Mutations in human PCLN1 are associated with familial hypomagnesemia with hypercalciuria and neph...
The purpose of this study was to determine the cellular and subcellular localization of aquaporin-8 (AQP8) in rat kidney and other organs by RT-PCR analyses and by immunoblotting and immunohistochemistry using peptide-derived rabbit antibodies to rat AQP8. RT-PCR and Southern blotting revealed the presence of AQP8 mRNA in all kidney zones. LLC-PK(1...
The discovery of aquaporin-1 (AQP1) by Agre and associates answered the longstanding biophysical question of how water specifically crosses biological membranes. In the kidney at least 7 aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration....
Diabetes mellitus (DM) is associated with osmotic diuresis and natriuresis. At day 15, rats with DM induced by streptozotocin (n = 13) had severe hyperglycemia (27.1 ± 0.4 vs. 4.7 ± 0.1 mM in controls) and had a fivefold increase in water intake (123 ± 5 vs. 25 ± 2 ml/day) and urine output. Semi-quantitative immunoblotting revealed a significant in...
The aims of this study were to determine the cellular and subcellular localization of aquaporin-9 (AQP9) in different rat organs by immunoblotting, immunohistochemistry and immunoelectron microscopy. To analyze this, we used rabbit antibodies to rat AQP9 raised against three different AQP9 peptides (amino acids 267-287, 274-295, and 278-295). In Co...
To establish the segmental, cellular, and subcellular localization of AQP7 in rat and mouse kidney, we used RT-PCR, immunocytochemical, and immunoblotting approaches. RT-PCR of rat and mouse kidney zones revealed AQP7 mRNA in cortex and outer stripe of the outer medulla. RT-PCR on microdissected nephron segments revealed AQP7 mRNA in proximal convo...
Transport of water and salt across cell membranes is of fundamental importance for all cellular function, and transport of water across epithelia in, among others, kidney, heart and lung is of great importance for the function of these organs. The molecular basis for transport of water across cell membranes was totally unknown until Peter Agre and...
