RELATIONSHIP BETWEEN SOMATOSTATIN RECEPTORS AND ACTIVATION OF HEPATIC STELLATE CELL

Objective To investigate the relationship between expression of somatostatin receptors(SSTRs) and activation of rat hepatic stellate cell (HSC). Methods HSCs were isolated from rats by in situ perfusion and single-step density gradient centrifugation, and then SSTR1-5 mRNA levels in the differentiated first passage HSCs were detected by means of reverse transcription polymerase chain reaction. On the other hand, hepatic fibrosis was induced in adult male Sprague-Dawley rats by carbon tetrachloride intoxication, and the expression of SSTR1-5 in normal as well as fibrotic liver was measured by immunohistochemical staining. Results SSTR mR-NA and SSTR could not be found in freshly isolated rat HSCs and normal rat liver. But SSTR1-3 mRNA appeared as HSCs became wholly activated, and SSTR1-3 could also be identified on the membrane of activated HSCs in the peri-sinusoid space, fibrous septa, etc. Conclusion The expression of SSTR1-3 in the rat HSC is closely related to its activation. This may reflect one of the main negative regulation mechanisms in the course of HSC activation.

Relationship between somatostatin receptors and activation of hepatic stellate cells

Background Somafostatin receptors (SSTRs) have been sug gested to involve in mediating the effect of somatostatin on hepatic stellate ce lls (HSCs) in an activation-dependent way. We, therefore, try to investigate th e relationship between expression of SSTRs and activation of rat HSCs.Methods HSCs were isolated from rats by in situ perfusion and single-step density gradient centrifugation.SSTR 1-5 mRNA levels in the differentiated first passage HSCs were detected by means of a reverse transcription polymerase chain reaction. On the other hand, hepatic fibrosis was induced in adult male Sprague-Dawley rats by carbon tetrachloride intoxication, and the expression of SSTR 1-5 in normal as well as fibrotic livers was measured by immunohistochemical staining.Results SSTR mRNA and SSTR could not be found in freshly isolated rat HSCs or normal rat liver. However, SSTR 1-3 mRNA appeared as HSCs became wholly activated, and could also be identified on the membrane of activated HSCs in the perisinusoid space, fibrous septa, etc.Conclusion The expression of SSTR 1-3 in the rat HSC is closely related to its activation. This may reflect one of the main negative regulation mechanisms in the course of HSC activation.

KRT17 Promotes the Activation of HSCs via EMT in Liver Fibrosis

Background and Aims:Although activation of hepatic stellate cells(HSCs)plays a central role in the development of liver fibrosis,the mechanism underlying the activation of HSCs remains unclear.Keratin 17(KRT17),a member of the intermediate filament family,can regulate tumor cell proliferation and migration.The current study aimed to elucidate the role of KRT17 in the activation of HSCs and the mechanisms underlying liver fibrosis.Methods:The expression of KRT17 was determined using immunohistochemistry in tissue microarray.Western blotting and qRT-PCR assays were used to determine the KRT17 expression in fibrotic liver tissues obtained from human subjects and mice.LX-2 cells were treated with TGF-β1 recombinant protein and adipocyte differentiation mixture(MDI)mix to induce and reverse LX-2 cell activation,respectively,in order to explore the correlation between KRT17 and HSC activation.Additionally,cell proliferation and migration abilities of LX-2 cells transfected with KRT17-overexpressing plasmid or small interfering RNA were determined using CCK-8,flow cytometry,Transwell,and wound healing assays.Finally,rescue assay was used to explore the role of KRT17 in HSC activation and epithelial-mesenchymal transition(EMT).Results:The expression of KRT17 was higher in the hu-man and mouse fibrotic liver tissues than in healthy liver tissues,and it was positively correlated with HSC activa-tion.Upregulated KRT17 enhanced proliferation,migration,HSC activation and EMT in LX-2 cells,while knockdown of KRT17 reversed these effects.TGF-β1 recombinant protein accelerated KRT17-mediated EMT,HSC activation and proliferation,while TGF-β1 inhibitor counteracted the effect of KRT17 in vitro.Conclusions:KRT17 promoted HSC activation,proliferation and EMT in hepatic fibrosis probably via TGF-β1 signaling,and KRT17 might serve as a therapeutic target for the treatment of liver fibrosis.