Leslie Gewin
Faculty Member
Last active: 3/26/2019

Pharmacologic Blockade of v1 Integrin Ameliorates Renal Failure and Fibrosis .

Chang Y, Lau WL, Jo H, Tsujino K, Gewin L, Reed NI, Atakilit A, Nunes ACF, DeGrado WF, Sheppard D
J Am Soc Nephrol. 2017 28 (7): 1998-2005

PMID: 28220032 · PMCID: PMC5491273 · DOI:10.1681/ASN.2015050585

Activated fibroblasts are deemed the main executors of organ fibrosis. However, regulation of the pathologic functions of these cells is poorly understood. PDGF receptor (PDGFR) is highly expressed in activated pericytes, a main source of fibroblasts. Studies using a PDGFR promoter-driven Cre system to delete v integrins in activated fibroblasts identified these integrins as core regulators of fibroblast activity across solid organs, including the kidneys. Here, we used the same PDGFR-Cre line to isolate and study renal fibroblasts We found that renal fibroblasts express three v integrins, namely v1, v3, and v5. Blockade of v1 prevented direct binding of fibroblasts to the latency-associated peptide of TGF-1 and prevented activation of the latent TGF- complex. Continuous administration of a recently described potent small molecule inhibitor of v1, 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 v1 integrin could thus hold promise as a therapeutic intervention in CKD characterized by renal fibrosis.

Copyright © 2017 by the American Society of Nephrology.

MeSH Terms (9)

Animals Fibrosis Guanidines Kidney Male Mice Receptors, Vitronectin Renal Insufficiency Sulfonamides

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