Beta ig-h3 promotes renal proximal tubular epithelial cell adhesion, migration and proliferation through the interaction with alpha3beta1 integrin.
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.
Park
Sun-Woo
SW
Cell and Matrix Biology National Research Laboratory, Department of Biochemistry, School of Medicine, Kyungpook national university, Jung-gu, Daegu, Korea.
Bae
Jong-Sup
JS
Kim
Ki-San
KS
Park
Sun-Hee
SH
Lee
Byung-Heon
BH
Choi
Je-Yong
JY
Park
Jae-Yong
JY
Ha
Sung-Woo
SW
Kim
Yong-Lim
YL
Kwon
Tae-Hwan
TH
Kim
In-San
IS
Park
Rang-Woon
RW
D020816:Amino Acid Motifs; D019138:Antibodies, Blocking / Q000276:immunology; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D039201:Integrin alpha3beta1 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D025941:Protein Interaction Mapping; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D000099222:betaIG-H3 Protein
D019138:Antibodies, Blocking; D016326:Extracellular Matrix Proteins; D039201:Integrin alpha3beta1; D010455:Peptides; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000099222:betaIG-H3 Protein; C508960:TGFB1 protein, human