| First Author | Lee K | Year | 2015 |
| Journal | J Am Soc Nephrol | Volume | 26 |
| Issue | 4 | Pages | 888-95 |
| PubMed ID | 25145933 | Mgi Jnum | J:232154 |
| Mgi Id | MGI:5776108 | Doi | 10.1681/ASN.2013111179 |
| Citation | Lee K, et al. (2015) Inactivation of integrin-beta1 prevents the development of polycystic kidney disease after the loss of polycystin-1. J Am Soc Nephrol 26(4):888-95 |
| abstractText | Dysregulation of polycystin-1 (PC1) leads to autosomal dominant polycystic kidney disease (ADPKD), a disorder characterized by the formation of multiple bilateral renal cysts, the progressive accumulation of extracellular matrix (ECM), and the development of tubulointerstitial fibrosis. Correspondingly, cystic epithelia express higher levels of integrins (ECM receptors that control various cellular responses, such as cell proliferation, migration, and survival) that are characteristically altered in cystic cells. To determine whether the altered expression of ECM and integrins could establish a pathologic autostimulatory loop, we tested the role of integrin-beta1 in vitro and on the cystic development of ADPKD in vivo. Compared with wild-type cells, PC1-depleted immortalized renal collecting duct cells had higher levels of integrin-beta1 and fibronectin and displayed increased integrin-mediated signaling in the presence of Mn(2+). In mice, conditional inactivation of integrin-beta1 in collecting ducts resulted in a dramatic inhibition of Pkd1-dependent cystogenesis with a concomitant suppression of fibrosis and preservation of normal renal function. Our data provide genetic evidence that a functional integrin-beta1 is required for the early events leading to renal cystogenesis in ADPKD and suggest that the integrin signaling pathway may be an effective therapeutic target for slowing disease progression. |
