Renal fibrosis is characterized by accumulation of extracellular matrix components and collagen deposition. TGF-β1 acts as a master switch promoting renal fibrosis through Smad dependent and/or Smad independent pathways. Thirty-five male C57BL/6 mice were divided into five groups of seven each; sham, unilateral ureteral obstruction (UUO), UUO+galunisertib (150 and 300 mg/kg/day), galunisertib (300 mg/kg/day). The UUO markedly induced renal fibrosis and injury as indicated by renal functional loss, increased levels of collagen Iα1, fibronectin and α-SMA; it also activated both the Smad 2/3 and MAPKs pathways as indicated by increased levels of TGF-β1, p-Smad 2, p-Smad 3, p-p38, p-JNK and p-ERK. These UUO-induced changes were markedly attenuated by oral administration of galunisertib, the TGFβRI small molecule inhibitor. In conclusion, we demonstrated that TGF-β1 receptor blockade can prevent UUO-induced renal fibrosis through indirect modulation of Smad and MAPKs signaling pathways and may be useful as a therapeutic agent in treatment and/or prevention of renal fibrosis.

肾纤维化的特征是细胞外基质成分的积累和胶原蛋白的沉积。TGF-β1 充当通过 Smad 依赖和/或 Smad 非依赖途径促进肾纤维化的主开关。将 35 只雄性 C57BL/6 小鼠分成 5 组，每组 7 只；假手术、单侧输尿管梗阻 (UUO)、UUO+galunisertib (150 和 300 mg/kg/天)、galunisertib (300 mg/kg/天)。UUO 显着诱导肾纤维化和损伤，表现为肾功能丧失、胶原蛋白 Iα1、纤连蛋白和 α-SMA 水平升高；它还激活了 Smad 2/3 和 MAPKs 途径，如 TGF-β1、p-Smad 2、p-Smad 3、p-p38、p-JNK 和 p-ERK 水平的增加所示。口服 TGFβRI 小分子抑制剂 galunisertib 可显着减弱这些 UUO 诱导的变化。综上所述，