Abstract
Betaig-h3 (betaig-h3) is a secretory protein composed of fasciclin I-like repeats containing sequences that allows binding of integrins and glycosaminoglycans in vivo. Expression of betaig-h3 is responsive to TGF-Beta and the protein is found to be associated with extracellular matrix (ECM) molecules, implicating betaig-h3 as an ECM adhesive protein of developmental processes. We previously observed predominant expression of betaig-h3 expression in the basement membrane of proximal tubules of kidney. In this study, the physiological relevance of such localized expression of betaig-h3 was examined in the renal proximal tubular epithelial cells (RPTEC). RPTEC constitutively expressed betaig-h3 and the expression was dramatically induced by exogenous TGF-Beta1 treatment. betaig-h3 and its second and fourth FAS1 domain were able to mediate RPTEC adhesion, spreading and migration. Two known alpha3beta1 integrin-interaction motifs including aspartatic acid and isoleucine residues, NKDIL and EPDIM in betaig-h3 were responsible to mediate RPTEC adhesion, spreading, and migration. By using specific antibodies against integrins, we confirmed that alpha3beta1 integrin mediates the adhesion and migration of RPTECs on betaig-h3. In addition, it also enhanced proliferation of RPTECs through NKDIL and EPDIM. These results indicate that betaig-h3 mediates adhesion, spreading, migration and proliferation of RPTECs through the interaction with alpha3beta1 integrin and is intimately involved in the maintenance and the regeneration of renal proximal tubular epithelium.
Highlights
Transforming growth factor-β (TGF-β) has potent effects on the proliferation and differentiation of a variety of cell types as well as on the synthesis of the extracellular matrix (ECM)
E x p re ss io n o f βig h3 is responsive to TGF-β and the protein is found to be associated with extracellular m atrix (E C M ) m o le cu les, im p lic a tin g βig -h 3 a s an E C M adhesive protein of developm ental processes
The physiological relevance of such localized expression of βig-h3 was exam ined in the renal proximal tubular epithelial cells (RPTEC)
Summary
Transforming growth factor-β (TGF-β) has potent effects on the proliferation and differentiation of a variety of cell types as well as on the synthesis of the extracellular matrix (ECM). Βig-h3 is a cell adhesive protein whose expression is highly induced by TGF-β in several cell types (Sharma & Ziyadeh, 1995). As βig-h3 has a function to mediate cell adhesion, migration, and proliferation and is highly induced by TGF-β, it may play some potential roles in renal tissue injury and/or regeneration. An in situ hybridization study has revealed that βig-h3 mRNA is expressed in proximal tubular epithelial cells ( in the S3 segment) and in the juxtaglomerular apparatus, and that these mRNA levels in the kidney are upregulated in diabetes mellitus induced by streptozotocin (Gilbert et al, 1998). The present study aims to elucidate the role of βig-h3 in proximal tubular epithelium and the effect of βig-h3 on adhesion, migration, and proliferation of renal proximal tubular epithelial cells (RPTECs) was investigated
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