Terminal differentiation of epithelia from trophectoderm to the intercalated cell: The role of hensin

The intercalated cells of the collecting tubules of mammalian kidneys were discovered by Haggege and Richet to change their morphology in response to a variety of physiologic stimuli related to changes in acid base status. Recent studies showed that the conversion of beta to alpha intercalated cell under the influence of acidification of the medium is due to the deposition of hensin in the extracellular matrix of these cells and activation of a novel inductive signal transduction pathway. The conversion of beta to alpha cells is shown to be a process of terminal differentiation. Hensin is secreted as a monomer, and activation of the cell induces two activities that convert it to a dimer by folding and into a fiber by bundling of the folded dimers by galectin 3. Only the fiber is functional. Hensin is expressed in most epithelial cells, and its staining pattern suggests that it might be involved in the terminal differentiation of most epithelia. There is loss of heterozygosity of hensin in a large number of epithelial and neural tumors, making it likely that it is a tumor suppressor gene.