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

摘要: 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 TGF-β-induced matrix production is mediated by fibroblasts, role of these cells TGF-β-dependent fibrosis following injury well defined. To address this, we deleted TGF-β type II receptor matrix-producing interstitial using two different inducible Cre models: COL1A2-Cre with a mesenchymal enhancer element and tenascin-Cre targets medullary cells, either mouse unilateral ureteral obstruction or aristolochic acid model. Renal lacking had significantly impaired collagen I production, but, unexpectedly, overall tissue was unchanged conditional knockouts after injury. Thus, abrogating signaling sufficient to reduce