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

ABSTRACT: Transforming growth factor-? (TGF-?) 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-?-induced matrix production is mediated by renal fibroblasts, the role of these cells in TGF-?-dependent tubulointerstitial fibrosis following renal injury is not well defined. To address this, we deleted the TGF-? 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-? receptor had significantly impaired collagen I production, but, unexpectedly, overall tissue fibrosis was unchanged in the conditional knockouts after renal injury. Thus, abrogating TGF-? signaling in matrix-producing interstitial cells is not sufficient to reduce fibrosis after renal injury.

SUBMITTER: Neelisetty S 

PROVIDER: S-EPMC4556568 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature