Differentiation of columnar epithelia: the hensin pathway.
ABSTRACT Epithelia, the most common variety of cells in complex organisms exist in many shapes. They are sheets of polarized cells that separate two compartments and selectively transport materials from one to the other. After acquiring these general characteristics, they differentiate to become specialized types such as squamous columnar or transitional epithelia. High density seeding converts a kidney-derived cell line from flat ;generic' epithelial cells to columnar cells. The cells acquire all the characteristics of differentiated columnar cells, including microvilli, and the capacity for apical endocytosis. The high seeding density induces the deposition of a new protein termed hensin and polymerization of hensin is the crucial event that dictates changes in epithelial phenotype. Hensin is widely expressed in most epithelia. Its deletion in mice leads to embryonic lethality at the time of generation of the first columnar epithelium, the visceral endoderm. Moreover many human cancers have deletions in the hensin gene, which indicates that it is a tumor suppressor.
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ABSTRACT: Acid–base transport in the renal collecting tubule is mediated by two canonical cell types: the β-intercalated cell secretes HCO3 by an apical Cl:HCO3 named pendrin and a basolateral vacuolar (V)-ATPase. Acid secretion is mediated by the α-intercalated cell, which has an apical V-ATPase and a basolateral Cl:HCO3 exchanger (kAE1). We previously suggested that the β-cell converts to the α-cell in response to acid feeding, a process that depended on the secretion and deposition of an extracellular matrix protein termed hensin (DMBT1). Here, we show that deletion of hensin from intercalated cells results in the absence of typical α-intercalated cells and the consequent development of complete distal renal tubular acidosis (dRTA). Essentially all of the intercalated cells in the cortex of the mutant mice are canonical β-type cells, with apical pendrin and basolateral or diffuse/bipolar V-ATPase. In the medulla, however, a previously undescribed cell type has been uncovered, which resembles the cortical β-intercalated cell in ultrastructure, but does not express pendrin. Polymerization and deposition of hensin (in response to acidosis) requires the activation of β1 integrin, and deletion of this gene from the intercalated cell caused a phenotype that was identical to the deletion of hensin itself, supporting its critical role in hensin function. Because previous studies suggested that the conversion of β- to α-intercalated cells is a manifestation of terminal differentiation, the present results demonstrate that this differentiation proceeds from HCO3 secreting to acid secreting phenotypes, a process that requires deposition of hensin in the ECM.Proceedings of the National Academy of Sciences 12/2010; 107(50):21872-21877. · 9.81 Impact Factor
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ABSTRACT: The uriniferous tubule is divided into the proximal tubule, the intermediate (thin) tubule, the distal tubule and the collecting duct. The present chapter is based on the chapters by Maunsbach and Christensen on the proximal tubule, and by Kaissling and Kriz on the distal tubule and collecting duct in the 1992 edition of the Handbook of Physiology, Renal Physiology. It describes the fine structure (light and electron microscopy) of the entire mammalian uriniferous tubule, mainly in rats, mice, and rabbits. The structural data are complemented by recent data on the location of the major transport- and transport-regulating proteins, revealed by morphological means(immunohistochemistry, immunofluorescence, and/or mRNA in situ hybridization). The structural differences along the uriniferous tubule strictly coincide with the distribution of the major luminal and basolateral transport proteins and receptors and both together provide the basis for the subdivision of the uriniferous tubule into functional subunits. Data on structural adaptation to defined functional changes in vivo and to genetical alterations of specified proteins involved in transepithelial transport importantly deepen our comprehension of the correlation of structure and function in the kidney, of the role of each segment or cell type in the overall renal function,and our understanding of renal pathophysiology.Comprehensive Physiology. 04/2012; 2(2):805-61.
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ABSTRACT: S5D-SRCRB is a novel mouse secretory glycoprotein belonging to the ancient and highly conserved scavenger receptor cysteine-rich superfamily of protein receptors. Available evidence indicates that S5D-SRCRB interacts with conserved microbial cell wall components, as well as with some endogenous proteins, and presents a restricted tissue expression pattern. This study further analyzes the expression of S5D-SRCRB along the mouse urogenital tract. Immunohistochemical staining for S5D-SRCRB was observed in spermatocytes from seminiferous tubules and in the epithelial surface from urethra and bladder, as well as in kidney tubules, mainly from medulla and papilla. Double stainings showed that S5D-SRCRB is expressed in both principal (P) and intercalated (IC) cells from renal collecting ducts (CD). By using an in vitro cell model of IC cell differentiation, preferential expression of S5D-SRCRB was observed in the apical border of terminally differentiated IC. Colocalization of S5D-SRCRB with galectin-3 (Gal-3) was also observed in kidney and bladder, but not in testis, supporting concurrent biochemical studies demonstrating the carbohydrate-dependent interaction of Gal-3 and S5D-SRCRB. Furthermore, upregulation of S5D-SRCRB expression was observed in in vitro and in vivo models of bacterial aggression, reinforcing the emerging view that CD, and specially IC, are important players in innate defense of the urinary tract against infection. Taken together, the results indicate that S5D-SRCRB is an integral component of the urogenital tract involved in innate immune functions.Tissue Antigens 04/2014; 83(4). · 2.35 Impact Factor