title: Study on the Antifibrotic Effects of Recombinant Shark Hepatical Stimulator Analogue (r-sHSA) in Vitro and in Vivo.
abstract: Hepatic fibrosis is an effusive wound healing process, characterized by an excessive deposition of extracellular matrix (ECM), as the consequence of chronic liver injury of any etiology. Current therapeutic repertoire for hepatic fibrosis is limited to withdrawal of the noxious agent, which is not always feasible. Hence, in this article, the antifibrotic effects and possible mechanisms of r-sHSA, a recombinant protein with hepatoprotection potential, were investigated. Using NIH/3T3 (mouse embro-fibroblast cell line), skin fibroblasts (human skin fibroblasts, SFBs) and HSC-T6 (rat hepatic stellate cell line), the in vitro effect of r-sHSA was evaluated by measuring the expression levels of alpha-1 Type I collagen (Col1A1) and α-smooth muscle actin (α-SMA). It turned out those fibrosis indicators were typically inhibited by r-sHSA, suggesting its capacity in HSCs inactivation. The antifibrotic activity of r-sHSA was further investigated in vivo on CCl4-induced hepatic fibrosis, in view of significant improvement of the biochemical and histological indicators. More specifically, CCl4-intoxication induced a significant increase in serological biomarkers, e.g., transaminase (AST, ALT), and alkaline phosphatase (ALP), as well as disturbed hepatic antioxidative status; most of the parameters were spontaneously ameliorated to a large extent by withdrawal of CCl4, although the fibrotic lesion was observed histologically. In contrast, r-sHSA treatment markedly eliminated fibrous deposits and restored architecture of the liver in a dose dependent manner, concomitantly with the phenomena of inflammation relief and HSCs deactivation. To sum up, these findings suggest a therapeutic potential for r-sHSA in hepatic fibrosis, though further studies are required.
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. wstarty@gmail.com.
authors: Ying
authors: Y
authors: Wang
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. oluckyo@126.com.
authors: Xiaoyuan
authors: X
authors: Zhang
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. yy05429@126.com.
authors: Yang
authors: Y
authors: Yang
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. rainbowyank@163.com.
authors: Xiaohong
authors: X
authors: Yang
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. yebp@cpu.edu.cn.
authors: Boping
authors: B
authors: Ye
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology*; D012754:Sharks / Q000378:metabolism*
chemical_list: D000199:Actins; D015415:Biomarkers; D024042:Collagen Type I; D011994:Recombinant Proteins
keywords: antifibrosis; carbon tetrachloride; hepatic fibrosis; hepatic stellate cells; r-sHSA