Renal fibrosis is not reduced by blocking transforming growth factor-[beta] signaling in matrix-producing interstitial cells

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 thes...

Full description

Saved in:
Bibliographic Details
Published in:Kidney international 2015-09, Vol.88 (3), p.503
Main Authors: Neelisetty, Surekha, Alford, Catherine, Reynolds, Karen, Woodbury, Luke, Nlandu-khodo, Stellor, Yang, Haichun, Fogo, Agnes B, Hao, Chuan-ming, Harris, Raymond C, Zent, Roy, Gewin, Leslie
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0085-2538
1523-1755
DOI:10.1038/ki.2015.51