Genistein alleviates pulmonary fibrosis by inactivating lung fibroblasts
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초록
Pulmonary fibrosis is a serious lung disease that occurs predominantlyin men. Genistein is an important natural soybeanderivedphytoestrogen that affects various biological functions,such as cell migration and fibrosis. However, the antifibroticeffects of genistein on pulmonary fibrosis are largely unknown. The antifibrotic effects of genistein were evaluated using invitro and in vivo models of lung fibrosis. Proteomic data wereanalyzed using nano-LC-ESI-MS/MS. Genistein significantly reducedtransforming growth factor (TGF)-β1-induced expressionof collagen type I and α-smooth muscle actin (SMA) in MRC-5cells and primary fibroblasts from patients with idiopathic pulmonaryfibrosis (IPF). Genistein also reduced TGF-β1-inducedexpression of p-Smad2/3 and p-p38 MAPK in fibroblast models. Comprehensive protein analysis confirmed that genistein exertedan anti-fibrotic effect by regulating various molecular mechanisms,such as unfolded protein response, epithelial mesenchymaltransition (EMT), mammalian target of rapamycin complex1 (mTORC1) signaling, cell death, and several metabolic pathways. Genistein was also found to decrease hydroxyprolinelevels in the lungs of BLM-treated mice. Genistein exerted ananti-fibrotic effect by preventing fibroblast activation, suggestingthat genistein could be developed as a pharmacological agentfor the prevention and treatment of pulmonary fibrosis.
Abstract
Pulmonary fibrosis is a serious lung disease that occurs predominantlyin men. Genistein is an important natural soybeanderivedphytoestrogen that affects various biological functions,such as cell migration and fibrosis. However, the antifibroticeffects of genistein on pulmonary fibrosis are largely unknown. The antifibrotic effects of genistein were evaluated using invitro and in vivo models of lung fibrosis. Proteomic data wereanalyzed using nano-LC-ESI-MS/MS. Genistein significantly reducedtransforming growth factor (TGF)-β1-induced expressionof collagen type I and α-smooth muscle actin (SMA) in MRC-5cells and primary fibroblasts from patients with idiopathic pulmonaryfibrosis (IPF). Genistein also reduced TGF-β1-inducedexpression of p-Smad2/3 and p-p38 MAPK in fibroblast models. Comprehensive protein analysis confirmed that genistein exertedan anti-fibrotic effect by regulating various molecular mechanisms,such as unfolded protein response, epithelial mesenchymaltransition (EMT), mammalian target of rapamycin complex1 (mTORC1) signaling, cell death, and several metabolic pathways. Genistein was also found to decrease hydroxyprolinelevels in the lungs of BLM-treated mice. Genistein exerted ananti-fibrotic effect by preventing fibroblast activation, suggestingthat genistein could be developed as a pharmacological agentfor the prevention and treatment of pulmonary fibrosis.
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