April 16, 2015

Surprising finding in the kidney

TGF-beta signaling in the kidney was thought to be a target for reducing renal fibrosis, but Vanderbilt researchers report that fibrosis still occurs in the absence of TGF-beta signaling.

by Barbara O’Brien

Progressive renal fibrosis is the common pathway whereby kidney injury of all causes leads to renal failure requiring dialysis or kidney transplantation. Thus, finding molecular targets for treatment of renal fibrosis is essential.

A major mediator of renal fibrosis is transforming growth factor-beta (TGF-beta) signaling. Interstitial cells that produce extracellular matrix are the cells thought to be responsible for TGF-beta-dependent fibrosis, making TGF-beta signaling in interstitial cells a potential target for reducing renal fibrosis.

However, fibrosis after renal injury was not reduced when the TGF-beta receptor was “knocked out” in interstitial cells in a mouse model, Leslie Gewin, M.D., and colleagues reported recently in the journal Kidney International. Blocking TGF-beta signaling in interstitial cells thus is not sufficient to reduce fibrosis, they concluded.

Clinical trials of TGF-beta inhibitors have been disappointing, implying that better understanding of how TGF-beta mediates response to injury and identification of additional components that contribute to fibrosis are critical for developing future therapeutic targets.

This research was supported by a Career Development Award from the Department of Veterans Affairs, by the Pediatric Nephrology Center of Excellence, VA Merit Awards and grants from the National Institutes of Health (DK051265, DK095785, DK083187, DK075594, DK069221).

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