Locostatin Alleviates Liver Fibrosis Induced by Carbon Tetrachloride in Mice
Background and Aims
Liver fibrosis is featured with excessive deposition of extracellular matrix and fibrous connective tissue hyperplasia. The specific inhibitor of Raf-1 kinase inhibitor protein, locostatin, inhibits the migration of hepatic stellate cells. In this study, we investigated the effect of locostatin on liver fibrosis and its underlying mechanism.
Carbon tetrachloride (CCl4) was used to induce liver fibrosis in mice, and locostatin was injected intraperitoneally. Liver fibrosis was assessed by Masson and Sirius red staining, hydroxyproline (HYP) assay, and collagen percentage area. Collagen I, collagen III, and α-SMA were detected by RT-PCR and western blot. The levels of MMP-13, MMP-2, TIMP-1, and TIMP-2 were estimated by ELISA. Liver inflammation was evaluated by HE staining and immunohistochemistry; liver myeloperoxidase (MPO), superoxide dismutase, and malondialdehyde were measured by ELISA; and cytokines were by Mouse Cytokine Array Q4000.
Compared to the CCl4 group, HYP (208.56 ± 6.12) µg/g, percentage of total collagen at overall region (1.91 ± 0.13), MMP-13/TIMP-1 (0.19 ± 0.01), MPO (1.45 ± 0.04) U/g, TGF-β (2652 ± 91.20), PDGF-AA (3897 ± 290.69), and E-selectin (1569 ± 66.48) in the liver tissues were decreased significantly in the locostatin-treated group.
Locostatin mitigated liver fibrosis and inflammation induced by CCl4. The mechanism is via inhibition inflammatory cytokines, TGF-β, PDGF-AA, and E-selectin.
KeywordsLocostatin Liver fibrosis Collagen Myeloperoxidase E-selectin
This work was supported by grants to JJM from the National Natural Science Foundation of China (No. 81200311), the National Natural Science Foundation of Hebei Province (China, H2015206431), the scientific research projects funded by talents engineering training in Hebei (China, A2016005065), the Hebei medical research key project (China, 20130184), and the Hebei youth talents project. The authors thank all the members of Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology.
Compliance with ethical standards
Conflict of interest
We declare that we have no conflict of interest on the paper.