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Betaig-h3 (βig-h3) is a secretory protein com-posed of fasciclin I-like repeats containing se-glycosaminoglycans in vivo. Expresion of βig- h3 is responsive to TGF-β and the protein is found to be asociated with extracelular matrix (ECM) molecules, implicating βig-h3 as an ECM adhesive protein of developmental processes. We previously observed predominant expres-sion of βig-h3 expresion in the basement mem-brane of proximal tubules of kidney. In this study, the physiological relevance of such lo-calized expression of βig-h3 was examined in the RPTEC constitutively expressed βig-h3 and the expression was dramatically induced by exo-genous TGF-β1 treatment. βig-h3 and its second and fourth FAS1 domain were able to mediate RPTEC adhesion, spreading and migration. Two known α3β1 integrin-interaction motifs including aspartatic acid and isoleucine residues, NKDIL and EPDIM in βig-h3 were responsible to medi-ate RPTEC adhesion, spreading, and migration. By using specific antibodies against integrins, we confirmed that α3β1 integrin mediates the adhesion and migration of RPTECs on βig-h3. In addition, it also enhanced proliferation of RPTECs through NKDIL and EPDIM. These re-sults indicate that βig-h3 mediates adhesion, spreading, migration and proliferation of RPTECs through the interaction with α3β1 integrin and is intimately involved in the maintenance and the regeneration of renal proximal tubular epi-thelium.

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