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The many talents of transforming growth factor-β in the kidney

Gewin, Lesliea,b,c

Current Opinion in Nephrology and Hypertension: May 2019 - Volume 28 - Issue 3 - p 203–210
doi: 10.1097/MNH.0000000000000490
RENAL IMMUNOLOGY AND PATHOLOGY: Edited by Agnes B. Fogo
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Purpose of review Preclinical data suggests that transforming growth factor-β (TGF-β) is arguably the most potent profibrotic growth factor in kidney injury. Despite this, recent clinical trials targeting TGF-β have been disappointing. These negative studies suggest that TGF-β signaling in the injured kidney might be more complicated than originally thought. This review examines recent studies that expand our understanding of how this pleiotropic growth factor affects renal injury.

Recent findings There are recent studies showing new mechanisms whereby TGF-β can mediate injury (e.g. epigenetic effects, macrophage chemoattractant). However, more significant are the increasing reports on cross-talk between TGF-β signaling and other pathways relevant to renal injury such as Wnt/β-catenin, YAP/TAZ (transcriptional coactivator with PDZ-binding motif), and klotho/FGF23. TGF-β clearly alters the response to injury, not just by direct transcriptional changes on target cells, but also through effects on other signaling pathways. In T cells and tubular epithelial cells, some of these TGF-β-mediated changes are potentially beneficial.

Summary It is unlikely that inhibition of TGF-β per se will be a successful antifibrotic strategy, but a better understanding of TGF-β's actions may reveal promising downstream targets or modulators of signaling to target therapeutically for chronic kidney disease.

aDivision of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center

bDepartment of Medicine, Veterans Affairs Hospital, Tennessee Valley Healthcare System

cDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA

Correspondence to Leslie Gewin, Room S3304 MCN, 1161 21st Avenue South, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Tel: +1 615 343-0767; fax: +1615 343-7156; e-mail: l.gewin@vumc.org

Received 1 December, 2018

Revised 15 December, 2018

Accepted 21 December, 2018

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