CTRP3 attenuates hepatic stellate cell activation through transforming growth factor-β/Smad signaling pathway.

Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of liver fibrosis. C1q/tumor necrosis factor-related protein 3 (CTRP3), a member of CTRPs, was involved in fibrosis. However, little is known about the role of CTRP3 in liver fibrosis. This study aimed to determine its role in liver fibrosis and explore the possible mechanism. Our results demonstrated that CTRP3 was lowly expressed in liver fibrosis tissues and activated HSCs. Overexpression of CTRP3 inhibited the proliferation and migration of HSCs, as well as suppressed the expression of extracellular matrix (ECM) in transforming growth factor-β1 (TGF-β1)-stimulated HSC-T6 cells. Furthermore, CTRP3 overexpression greatly inhibited the expression level of phosphorylation of Smad3 in TGF-β1-stimulated HSC-T6 cells. In conclusion, the present study demonstrated that CTRP3 inhibited the proliferation and migration of TGF-β1-induced HSC-T6 cells and attenuated liver fibrosis, at least in part, through inhibiting the Smad signaling pathway. These findings suggest that CTRP3 may be a promising therapeutic target for the treatment of liver fibrosis.

Cheng C ，Yu S ，Kong R ，Yuan Q ，Ma Y ，Yang W ，Cao G ，Xie L ... -  《-》

Glaucocalyxin A Attenuates the Activation of Hepatic Stellate Cells Through the TGF-β1/Smad Signaling Pathway.

Dong Z ，Gao Q ，Guo H 《-》

Scoparone attenuates hepatic stellate cell activation through inhibiting TGF-β/Smad signaling pathway.

Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. Scoparone, a major constituent isolated from Artemisia capillaris, was reported to possess hepatoprotective effect. However, the role of scoparone in liver fibrosis remains unknown. In the present study, we investigated the effects of scoparone on liver fibrosis in HSCs. Our results demonstrated that scoparoene inhibited the proliferation of HSCs exposed to transforming growth factor (TGF)-β1. In addition, scoparoene significantly suppressed TGF-β1-induced the expression of α-smooth muscle actin (α-SMA) and collagen I in HSC-T6 cells, as well as attenuated the expression of NADPH oxidase (NOX) isoforms expression and ROS production in TGF-β1-stimialted HSC-T6 cells. Mechanistically, scoparoene suppressed the phosphorylation level of Smad3 in TGF-β1-stimialted HSC-T6 cells. In conclusion, these findings showed that scoparone significantly inhibited the proliferation and activation of HSCs through the inactivation of TGF-β/Smad signaling pathway. These data provide that scoparone may have potential to treat liver fibrosis.

Liu X ，Zhao X 《-》

Sauchinone attenuates liver fibrosis and hepatic stellate cell activation through TGF-β/Smad signaling pathway.

Hepatic stellate cells (HSCs) are key mediators of fibrogenesis, and the regulation of their activation is now viewed as an attractive target for the treatment of liver fibrosis. Here, the authors investigated the ability of sauchinone, an active lignan found in Saururus chinensis, to regulate the activation of HSCs, to prevent liver fibrosis, and to inhibit oxidative stress in vivo and in vitro. Blood biochemistry and histopathology were assessed in CCl4-induced mouse model of liver fibrosis to investigate the effects of sauchinone. In addition, transforming growth factor-β1 (TGF-β1)-activated LX-2 cells (a human HSC line) were used to investigate the in vitro effects of sauchinone. Sauchinone significantly inhibited liver fibrosis, as indicated by decreases in regions of hepatic degeneration, inflammatory cell infiltration, and the intensity of α-smooth muscle actin staining in mice. Sauchinone blocked the TGF-β1-induced phosphorylation of Smad 2/3 and the transcript levels of plasminogen activator inhibitor-1 and matrix metalloproteinase-2 as well as autophagy in HSCs. Furthermore, sauchinone inhibited oxidative stress, as assessed by stainings of 4-hydroxynonenal and nitrotyrosine: these events may have a role in its inhibitory effects on HSCs activation. Sauchinone attenuated CCl4-induced liver fibrosis and TGF-β1-induced HSCs activation, which might be, at least in part, mediated by suppressing autophagy and oxidative stress in HSCs.

Lee JH ，Jang EJ ，Seo HL ，Ku SK ，Lee JR ，Shin SS ，Park SD ，Kim SC ，Kim YW ... -  《-》

Periostin down-regulation attenuates the pro-fibrogenic response of hepatic stellate cells induced by TGF-β1.

Liver fibrosis is characterized by an exacerbated accumulation of deposition of the extracellular matrix (ECM), and the activation of hepatic stellate cells (HSC) plays a pivotal role in the development of liver fibrosis. Periostin has been shown to regulate cell adhesion, proliferation, migration and apoptosis; however, the involvement of periostin and its role in transforming growth factor (TGF)-β1-induced HSC activation remains unclear. We used RT-PCR and Western blot to evaluate the expression level of periostin in hepatic fibrosis tissues and HSCs, respectively. Cell proliferation was determined using the Cell Proliferation ELISA BrdU kit, cell cycle was analysed by flow cytometry. The expression of α-smooth muscle actin (α-SMA), collagen I, TGF-β1, p-Smad2 and p-Smad3 were determined by western blot. Our study found that periostin was up-regulated in liver fibrotic tissues and activated HSCs. In addition, siRNA-periostin suppressed TGF-β1-induced HSC proliferation. The HSC transfected with siRNA-periostin significantly inhibited TGF-β1-induced expression levels of α-SMA and collagen I. Furthermore, TGF-β1 stimulated the expression of periostin, and siRNA-periostin attenuated TGF-β1-induced Smad2/3 activation in HSCs. These results suggest that periostin may function as a novel regulator to modulate HSC activation, potentially by promoting the TGF-β1/Smad signalling pathway, and propose a strategy to target periostin for the treatment of liver fibrosis.

Hong L ，Shejiao D ，Fenrong C ，Gang Z ，Lei D ... -  《-》