| First Author | Chang Y | Year | 2017 |
| Journal | J Am Soc Nephrol | Volume | 28 |
| Issue | 7 | Pages | 1998-2005 |
| PubMed ID | 28220032 | Mgi Jnum | J:293571 |
| Mgi Id | MGI:6437583 | Doi | 10.1681/ASN.2015050585 |
| Citation | Chang Y, et al. (2017) Pharmacologic Blockade of alphavbeta1 Integrin Ameliorates Renal Failure and Fibrosis In Vivo. J Am Soc Nephrol 28(7):1998-2005 |
| abstractText | Activated fibroblasts are deemed the main executors of organ fibrosis. However, regulation of the pathologic functions of these cells in vivo is poorly understood. PDGF receptor beta (PDGFRbeta) is highly expressed in activated pericytes, a main source of fibroblasts. Studies using a PDGFRbeta promoter-driven Cre system to delete alphav integrins in activated fibroblasts identified these integrins as core regulators of fibroblast activity across solid organs, including the kidneys. Here, we used the same PDGFRbeta-Cre line to isolate and study renal fibroblasts ex vivo We found that renal fibroblasts express three alphav integrins, namely alphavbeta1, alphavbeta3, and alphavbeta5. Blockade of alphavbeta1 prevented direct binding of fibroblasts to the latency-associated peptide of TGF-beta1 and prevented activation of the latent TGF-beta complex. Continuous administration of a recently described potent small molecule inhibitor of alphavbeta1, compound 8, starting the day of unilateral ureteral obstruction operation, inhibited collagen deposition in the kidneys of mice 14 days later. Compound 8 also effectively attenuated renal failure, as measured by BUN levels in mice fed an adenine diet known to cause renal injury followed by fibrosis. Inhibition of alphavbeta1 integrin could thus hold promise as a therapeutic intervention in CKD characterized by renal fibrosis. |
