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Locostatin Alleviates Liver Fibrosis Induced by Carbon Tetrachloride in Mice.
Dig Dis Sci. 2019 09; 64(9):2570-2580.DD

Abstract

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

Locostatin mitigated liver fibrosis and inflammation induced by CCl4. The mechanism is via inhibition inflammatory cytokines, TGF-β, PDGF-AA, and E-selectin.

Authors+Show Affiliations

Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei, China. majunji@hebmu.edu.cn.Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei, China.Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei, China.Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei, China.Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei, China.Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30874989

Citation

Ma, Junji, et al. "Locostatin Alleviates Liver Fibrosis Induced By Carbon Tetrachloride in Mice." Digestive Diseases and Sciences, vol. 64, no. 9, 2019, pp. 2570-2580.
Ma J, Qiu Y, Wang M, et al. Locostatin Alleviates Liver Fibrosis Induced by Carbon Tetrachloride in Mice. Dig Dis Sci. 2019;64(9):2570-2580.
Ma, J., Qiu, Y., Wang, M., Zhang, M., Zhao, X., & Jiang, H. (2019). Locostatin Alleviates Liver Fibrosis Induced by Carbon Tetrachloride in Mice. Digestive Diseases and Sciences, 64(9), 2570-2580. https://doi.org/10.1007/s10620-019-05588-5
Ma J, et al. Locostatin Alleviates Liver Fibrosis Induced By Carbon Tetrachloride in Mice. Dig Dis Sci. 2019;64(9):2570-2580. PubMed PMID: 30874989.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Locostatin Alleviates Liver Fibrosis Induced by Carbon Tetrachloride in Mice. AU - Ma,Junji, AU - Qiu,Yuzi, AU - Wang,Min, AU - Zhang,Ming, AU - Zhao,Xiaoyi, AU - Jiang,Huiqing, Y1 - 2019/03/14/ PY - 2018/07/16/received PY - 2019/03/08/accepted PY - 2019/3/16/pubmed PY - 2020/3/24/medline PY - 2019/3/16/entrez KW - Collagen KW - E-selectin KW - Liver fibrosis KW - Locostatin KW - Myeloperoxidase SP - 2570 EP - 2580 JF - Digestive diseases and sciences JO - Dig Dis Sci VL - 64 IS - 9 N2 - 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Locostatin mitigated liver fibrosis and inflammation induced by CCl4. The mechanism is via inhibition inflammatory cytokines, TGF-β, PDGF-AA, and E-selectin. SN - 1573-2568 UR - https://www.unboundmedicine.com/medline/citation/30874989/Locostatin_Alleviates_Liver_Fibrosis_Induced_by_Carbon_Tetrachloride_in_Mice_ DB - PRIME DP - Unbound Medicine ER -