Inhibition of hepatic stellate cell activation and liver fibrosis by fat-specific protein 27

Abstract

In order to explore the effects of fat-specific protein 27 (Fsp27) on regulation of hepatic stellate cell (HSC) activation and liver fibrosis. HSCs were isolated from rat liver tissues and cultivated in vitro for gene expression and lentivirus infection. CCK-8 cell viability assay, immunofluorescence staining, qRT-PCR, and western blot assays were used to assess phenotypic changes and gene expression in HSCs. The rat liver fibrosis model was produced by intraperitoneal injection of carbon tetrachloride for assessing the effects of Fsp27 in the rat liver. Gene expression was then detected by immunohistochemistry and ELISA assays. The results of the study showed that Fsp27 was constitutively expressed in primary quiescent HSCs, but was absent in activated HSCs. Ectopic expression of Fsp27 significantly inhibited HSC proliferation and activation, as well as expression of α-smooth muscle actin. Fsp27 expression also significantly reduced collagen I production and matrix metalloproteinases 2 protein levels, and to a lesser degree, reduced tissue inhibitors of metalloproteinases 1 expression. In vivo data showed that ectopic expression of Fsp27 protein significantly reduced levels of hydroxyproline in liver tissue, and decreased serum levels of collagen III and hyaluronic acid, which in turn, suppressed liver fibrosis in rats. From these findings, it can be concluded that Fsp27 expression suppressed HSC activation in vitro and liver fibrogenesis in vivo. Further studies are needed to explore whether expression of Fsp27 can be selected as a potential novel strategy for anti-fibrotic therapy against liver fibrosis.

Molecular Pathways: Targeting the Microenvironment of Liver Metastases

“…Calcipotriol, a low-calcemic analog of calcitriol and agonist of VDR was shown to restrict the fibrogenic response of aHepSC by reducing SMAD3 occupancy at profibrotic target genes via chromatin remodeling (55). Although validated in the context of experimental fibrosis, these, and other inhibitors that target the process of HepSC activation (56–59) could potentially have beneficial anti-metastatic effects by blocking early events in LM and their evaluation in this context is therefore warranted.…”

Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro

“…The animals were sacrificed by intraperitoneal injection of 3% pentobarbital sodium (60 mg/kg body weight, purchased from Beijing Propbs Biotechnology Co., Ltd.). The cell isolation method used was as previously described (16). Isolated HSCs were cultured in DMEM with L-glutamine and 10% FBS.…”

“…The final concentrations of bilirubin were 0, 1, 10 and 20 mg/l, with five replicates per concentration. After treatment for 24 h, 80 µl CCK-8 solution was added to each well and incubated for 2 h. The absorbance was read at a wavelength of 450 nm using a plate reader, and cell proliferation rates were calculated as previously described (16). …”

Specific Overexpression of Mitofusin-2 in Hepatic Stellate Cells Ameliorates Liver Fibrosis in Mice Model

“…1 Inhibition of HSC activation has been demonstrated to be a promising strategy to treat liver fibrosis. 12,13 Extensive studies have been performed to understand the mechanisms underlying regulation of HSC activation.…”