Deletion of hensin/DMBT1 blocks conversion of β- to α-intercalated cells and induces distal renal tubular acidosis

• DOI: 10.1073/pnas.1010364107
• Publication Date: 2010-11-23T05:41:46Z
• Authors: XiaoBo Gao; Dominique Eladari; Francoise Leviel; Ben Yi Tew; Cristina Miró-Julià; Faisal H. Cheema; Lance Miller; Raoul Nelson; Teodor G. Păunescu; Mary McKee; Dennis Brown; Qais Al-Awqati
• Keywords: Intercalated Cell; Pendrin; Cell type; Epithelial polarity

Acid–base transport in the renal collecting tubule is mediated by two canonical cell types: β-intercalated secretes HCO 3 an apical Cl:HCO named pendrin and a basolateral vacuolar (V)-ATPase. Acid secretion α-intercalated cell, which has V-ATPase exchanger (kAE1). We previously suggested that β-cell converts to α-cell response acid feeding, process depended on deposition of extracellular matrix protein termed hensin (DMBT1). Here, we show deletion from intercalated cells results absence typical consequent development complete distal tubular acidosis (dRTA). Essentially all cortex mutant mice are β-type cells, with or diffuse/bipolar V-ATPase. In medulla, however, undescribed type been uncovered, resembles cortical ultrastructure, but does not express pendrin. Polymerization (in acidosis) requires activation β1 integrin, this gene caused phenotype was identical itself, supporting its critical role function. Because previous studies conversion β- manifestation terminal differentiation, present demonstrate differentiation proceeds secreting phenotypes, ECM.