The quantitative proteomic analysis reveals schisantherin a prevents liver fibrosis through regulating extracellular matrix organization

The activation of hepatic stellate cell (HSC) induced by transforming growth factor-01 (TGF-01) is the key event in the pathogenesis of liver fibrosis. Schisantherin A (SCA), a main active ingredient of Schisandra chinensis, has anti-tumor and anti-inflammatory activities. Here, we reported that SCA inhibited the activation, proliferation, and cell cycle of human HSC cell line LX2. Then, by performing the tandem mass tag (TMT)-based quantitative proteomic analysis on LX2, we identified a total of 6045 proteins across the control, TGF-01-activated and SCA treated LX2 groups, of which 544 proteins were significantly changed among the three groups. All the differentially expressed proteins (DEPs) were assigned to 4 clusters by fuzzy c-means (FCM) clustering analysis. The changed expression of DEPs in cluster 3 and 4 was reversed by SCA treatment. Bioinformatic analysis revealed that SCA regulated the expression of several DEPs involved in extracellular matrix organization, such as thrombospondin 1 (THBS1), transgelin (TAGLN) and tissue inhibitor of metalloproteinase 3 (TIMP3). The Western blot and RT-qPCR analysis confirmed these proteins increased in TGF-01 group and decreased by the SCA treatment. In summary, we found that SCA may exert anti-fibrotic effect on HSCs by regulating the process of extracellular matrix organization in HSCs. Keywords: liver fibrosis, schisantherin A, proteomics, extracellular matrix organization. (C) 2022 Elsevier B.V. All rights reserved.