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

S Neelisetty, C Alford, K Reynolds, L Woodbury… - Kidney international, 2015 - Elsevier
S Neelisetty, C Alford, K Reynolds, L Woodbury, S Nlandu-Khodo, H Yang, AB Fogo
Kidney international, 2015Elsevier
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 …
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.
Elsevier