Beta ig-h3 promotes renal proximal tubular epithelial cell adhesion, migration and proliferation through the interaction with [alpha]3[beta]1 integrin

• Published in: Experimental & molecular medicine Vol. 36; no. 3; p. 211
• Main Authors: Park, Sun-woo, Bae, Jong-sup, Kim, Ki-san, Park, Sun-hee, Lee, Byung-heon, Choi, Je-yong, Park, Jae-yong, Ha, Sung-woo, Kim, Yong-lim, Kwon, Tae-hwan, Kim, In-san, Park, Rang-woon
• Format: Journal Article
• Language: English
• Published: Seoul Springer Nature B.V 01.06.2004
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/emm.2004.29

Betaig-h3 (βig-h3) is a secretory protein composed of fasciclin I-like repeats containing sequences that allows binding of integrins and glycosaminoglycans in vivo. Expression of βig-h3 is responsive to TGF-β and the protein is found to be associated with extracellular matrix (ECM) molecules, implicating βig-h3 as an ECM adhesive protein of developmental processes. We previously observed predominant expression of βig-h3 expression in the basement membrane of proximal tubules of kidney. In this study, the physiological relevance of such localized expression of βig-h3 was examined in the renal proximal tubular epithelial cells (RPTEC). RPTEC constitutively expressed βig-h3 and the expression was dramatically induced by exogenous 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 mediate 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 results 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 epithelium.