Exp Mol Med.  2004 Jun;36(3):211-219.

Beta ig-h3 promotes renal proximal tubular epithelial cell adhesion, migration and proliferation through the interaction with alpha3beta1 integrin

• Park SW
• Bae JS
• Kim KS
• Park SH
• Lee BH
• Choi JY
• Park JY
• Ha SW
• Kim YL
• Kwon TH
• Kim IS
• Park RW

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.

Keyword

adhesion; alpha3beta1 integrin; betaig-h3; migration; proliferation; renal proximal tubular epithelial cell

MeSH Terms

Amino Acid Motifs
Antibodies, Blocking/immunology
Cell Adhesion/physiology
Cell Movement/physiology
Cell Proliferation
Cells, Cultured
Epithelial Cells/drug effects
Extracellular Matrix Proteins/chemistry/immunology/*metabolism
Humans
Integrin alpha3beta1/chemistry/immunology/*metabolism
Kidney Tubules, Proximal/cytology/metabolism/*physiology
Peptides/chemistry/metabolism
Protein Interaction Mapping
Research Support, Non-U.S. Gov't
Transforming Growth Factor beta/chemistry/immunology/*metabolism/pharmacology