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Digestive Diseases and Sciences

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14.03.2019 | Original Article

Locostatin Alleviates Liver Fibrosis Induced by Carbon Tetrachloride in Mice

verfasst von: Junji Ma, Yuzi Qiu, Min Wang, Ming Zhang, Xiaoyi Zhao, Huiqing Jiang

Erschienen in: Digestive Diseases and Sciences | Ausgabe 9/2019

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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.

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Titel: Locostatin Alleviates Liver Fibrosis Induced by Carbon Tetrachloride in Mice
verfasst von: Junji Ma
Yuzi Qiu
Min Wang
Ming Zhang
Xiaoyi Zhao
Huiqing Jiang
Publikationsdatum: 14.03.2019
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 9/2019
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-019-05588-5

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Locostatin Alleviates Liver Fibrosis Induced by Carbon Tetrachloride in Mice

Abstract

Background and Aims

Methods

Results

Conclusions

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