Leslie Gewin
Faculty Member
Last active: 3/18/2020

Renal fibrosis is not reduced by blocking transforming growth factor-β signaling in matrix-producing interstitial cells.

Neelisetty S, Alford C, Reynolds K, Woodbury L, Nlandu-Khodo S, Yang H, Fogo AB, Hao CM, Harris RC, Zent R, Gewin L
Kidney Int. 2015 88 (3): 503-14

PMID: 25760325 · PMCID: PMC4556568 · DOI:10.1038/ki.2015.51

Transforming growth factor-β (TGF-β) strongly promotes renal tubulointerstitial fibrosis, but the cellular target that mediates its profibrotic actions has not been clearly identified. While in vitro data suggest that TGF-β-induced matrix production is mediated by renal fibroblasts, the role of these cells in TGF-β-dependent tubulointerstitial fibrosis following renal injury is not well defined. To address this, we deleted the TGF-β type II receptor in matrix-producing interstitial cells using two different inducible Cre models: COL1A2-Cre with a mesenchymal enhancer element and tenascin-Cre that targets medullary interstitial cells, and either the mouse unilateral ureteral obstruction or the aristolochic acid renal injury model. Renal interstitial cells lacking the TGF-β receptor had significantly impaired collagen I production, but, unexpectedly, overall tissue fibrosis was unchanged in the conditional knockouts after renal injury. Thus, abrogating TGF-β signaling in matrix-producing interstitial cells is not sufficient to reduce fibrosis after renal injury.

MeSH Terms (20)

Actins Animals Aristolochic Acids Cells, Cultured Collagen Type I Disease Models, Animal Extracellular Matrix Fibrosis Kidney Kidney Diseases Mice, Inbred C57BL Mice, Knockout Protein-Serine-Threonine Kinases Receptor, Platelet-Derived Growth Factor beta Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta Signal Transduction Time Factors Transforming Growth Factor beta Ureteral Obstruction

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