In heart disease, transforming growth factor-β1 （TGF-β1） converts fibroblasts into myofibroblasts, which synthesize and se- crete fibrillar type I and III collagens. The purpose of the present study was to investi...In heart disease, transforming growth factor-β1 （TGF-β1） converts fibroblasts into myofibroblasts, which synthesize and se- crete fibrillar type I and III collagens. The purpose of the present study was to investigate how hydrogen sulfide （HzS） sup- presses TGF-~l-induced differentiation of human cardiac fibroblasts to myofibroblasts. Human cardiac fibroblasts were se- rum-starved in fibroblast medium for 16 h before exposure to TGF-β1 （10 ng mL-1） for 24 h with or without sodium hydrosul- fide （NariS, 100 μmol L-1, 30 min pretreatment） treatment. NariS, an exogenous HzS donor, potently inhibited the prolifera- tion and migration of TGF-β1-induced human cardiac fibroblasts and regulated their cell cycle progression. Furthermore, NariS treatment led to suppression of fibroblast differentiation into myofibroblasts, and reduced the levels of collagen, TGF-β1, and activated Smad3 in TGF-β1-induced human cardiac fibroblasts in vitro. We therefore conclude that H2S sup- presses TGF-β1-stimulated conversion of fibroblasts to myofibroblasts by inhibiting the TGF-β1/Smad3 signaling pathway, as well as by inhibiting the proliferation, migration, and cell cycle progression of human cardiac myofibroblasts. These effects of H2S may play significant roles in cardiac remodeling associated with heart failure.展开更多
基金supported by the State Key Program of National Natural Science of China(81230007)
文摘In heart disease, transforming growth factor-β1 （TGF-β1） converts fibroblasts into myofibroblasts, which synthesize and se- crete fibrillar type I and III collagens. The purpose of the present study was to investigate how hydrogen sulfide （HzS） sup- presses TGF-~l-induced differentiation of human cardiac fibroblasts to myofibroblasts. Human cardiac fibroblasts were se- rum-starved in fibroblast medium for 16 h before exposure to TGF-β1 （10 ng mL-1） for 24 h with or without sodium hydrosul- fide （NariS, 100 μmol L-1, 30 min pretreatment） treatment. NariS, an exogenous HzS donor, potently inhibited the prolifera- tion and migration of TGF-β1-induced human cardiac fibroblasts and regulated their cell cycle progression. Furthermore, NariS treatment led to suppression of fibroblast differentiation into myofibroblasts, and reduced the levels of collagen, TGF-β1, and activated Smad3 in TGF-β1-induced human cardiac fibroblasts in vitro. We therefore conclude that H2S sup- presses TGF-β1-stimulated conversion of fibroblasts to myofibroblasts by inhibiting the TGF-β1/Smad3 signaling pathway, as well as by inhibiting the proliferation, migration, and cell cycle progression of human cardiac myofibroblasts. These effects of H2S may play significant roles in cardiac remodeling associated with heart failure.
