Beta ig-h3 promotes renal proximal tubular epithelial cell adhesion, migration and proliferation through the interaction with α3β1 integrin

Abstract

A bstract B etaig-h3 (βig-h3) is a secretory pro tein compo sed of fasciclin I-like repeats con tainin g sequ en ces that allo w s bind ing of integrins and glycosam in oglycan s in vivo . E xpression of βig -h3 is respon sive to T G F-β an d the p rotein is found to be associated w ith extracellular m atrix (E C M ) m o lecu les, im p licatin g βig-h3 as an E C M adhesive pro tein o f d evelopm ental processes. W e p reviou sly observed p red om inant expression of βig-h3 expression in the basem ent m embrane o f proxim al tubu les o f kid ney. In this stu dy, the p hysio logical relevance of su ch localized expression of βig-h3 was exam ined in the renal proxim al tubular epithelial cells (RPTEC). R P T E C constitu tively exp ressed βig -h 3 and the exp ression w as dram atically ind uced b y exogenous TG F-β1 treatm ent. βig-h3 and its second and fou rth F A S 1 dom ain w ere able to m ed iate R P TE C adhesion, spreading and m igration. Tw o know n α3β1 integrin-interaction m otifs including aspartatic acid and isoleucine resid ues, N K D IL an d E P D IM in βig -h 3 w ere resp o n sib le to m ed iate R P T E C ad hesio n, sp readin g, an d m igratio n. B y using specific an tib odies against in tegrin s, w e confirm ed that α3 β1 in teg rin m ed iates th e adh esion and m ig ration of R P T E C s on βig -h 3. In ad dition, it also en hanced proliferation of R P TE C s th roug h N K D IL and E P D IM . These results ind icate th at βig-h3 m ediates adh esion , spreading, m igration and proliferation of R P TE C s th ro u g h th e in teractio n w ith α3β1 in teg rin an d is in tim ately in vo lved in th e m ain ten an ce an d the regeneratio n o f ren al proxim al tubu lar ep ith eliu m .

βig-h3 triggers signaling pathways mediating adhesion and migration of vascular smooth muscle cells through αvβ5 integrin

“…Migration of fibroblasts on βig-h3 is also facilitated through the αvβ5 integrin . On the other hand, βig-h3 promotes migration of keratinocytes and renal tubular epithelial cells through the α3β1 integrin (Bae et al, 2002;Park et al, 2004). Furthermore, we recently reported that βig-h3 promotes the migration …”

“…βig-h3 plays a role in cell adhesion, migration, and wound healing (LeBaron et al, 1995;Bae et al, 2002;Park et al, 2004). In addition, βig-h3 is involved in certain human diseases.…”

MoFLP1, encoding a novel fungal fasciclin-like protein, is involved in conidiation and pathogenicity in Magnaporthe oryzae

“…First, deletion of MoFLP1 gene resulted in a significant reduction of conidial adhesion to the hydrophobic surface of GelBond. In animals, it has been suggested that fasciclin/βig-h3 may act as a cell adhesion substrate (Park et al, 2004) and promote cell attachment activity (Sato et al, 2004). In plants, fasciclin-like arabinogalactan proteins have been implicated to be associated with plant growth and development in various processes, including embryogenesis, cell adhesion, and cell proliferation (Schultz et al, 2000;Johnson et al, 2003).…”

T-CAM, a fastatin-FIII 9-10 fusion protein, potently enhances anti-angiogenic and anti-tumor activity αvβ3 and α5β1 integrins

“…The FAS1 domains have been identified in the secretory and membrane proteins of many organisms including mammals, insect, sea urchins, plants, yeast and bacteria . The FAS1 domain mediates cell adhesion and migration via interactions with different integrins (Kim et al, 2000a;Park et al, 2004;Lee et al, 2005;Thapa et al, 2007). Currently, only four FAS1 domain-containing human proteins have been identified (βig-h3, periostin, stabilin-1 and stabilin-2) and investigation of physiological and/or pathological source of fastatin and its regulatory mechanism has been the topic of intense investigation .…”