Tags

Type your tag names separated by a space and hit enter

Metformin mitigates carbon tetrachloride-induced TGF-β1/Smad3 signaling and liver fibrosis in mice.
Biomed Pharmacother. 2017 Jun; 90:421-426.BP

Abstract

Increasing evidence suggests that the widely used antidiabetic drug metformin have an extensive therapeutic range beyond hypoglycemic therapy. We previously found that metformin significantly attenuated acute hepatitis. The present study investigated the potential effects of metformin on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. The results indicated that treatment with metformin suppressed CCl4-induced elevation of liver index, formation of fibrotic septa, accumulation of connective tissue and upregulation of collagen I. These effects were not associated with increase of the antioxidative transcription factor nuclear erythroid 2-related factor 2 (NRF2) or its downstream targets, heme oxygenase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). However, treatment with metformin suppressed CCl4-induced expression of transforming growth factor beta 1 (TGF-β1) and phosphorylation of Smad3, which was accompanied with decreased level of alpha smooth muscle actin (α-SMA), a marker for the activated hepatic stellate cells (HSCs). These data indicates that metformin could mitigate CCl4-induced liver fibrosis and these beneficial effects might result from suppressed TGF-β1/Smad3 signaling.

Authors+Show Affiliations

Department of Pathophysiology, Chongqing Medical University, Chongqing, China.Department of Pathophysiology, Chongqing Medical University, Chongqing, China.Department of Pathophysiology, Chongqing Medical University, Chongqing, China.Department of Pathophysiology, Chongqing Medical University, Chongqing, China.Hospital of Chongqing University of Arts and Sciences, Chongqing, China.Department of Pharmacy, Chongqing Armed Corps Police Hospital, Chongqing, China.Department of Pathophysiology, Chongqing Medical University, Chongqing, China.Department of Pathophysiology, Chongqing Medical University, Chongqing, China. Electronic address: zhangli@cqmu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28390311

Citation

Fan, Kerui, et al. "Metformin Mitigates Carbon Tetrachloride-induced TGF-β1/Smad3 Signaling and Liver Fibrosis in Mice." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 90, 2017, pp. 421-426.
Fan K, Wu K, Lin L, et al. Metformin mitigates carbon tetrachloride-induced TGF-β1/Smad3 signaling and liver fibrosis in mice. Biomed Pharmacother. 2017;90:421-426.
Fan, K., Wu, K., Lin, L., Ge, P., Dai, J., He, X., Hu, K., & Zhang, L. (2017). Metformin mitigates carbon tetrachloride-induced TGF-β1/Smad3 signaling and liver fibrosis in mice. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 90, 421-426. https://doi.org/10.1016/j.biopha.2017.03.079
Fan K, et al. Metformin Mitigates Carbon Tetrachloride-induced TGF-β1/Smad3 Signaling and Liver Fibrosis in Mice. Biomed Pharmacother. 2017;90:421-426. PubMed PMID: 28390311.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metformin mitigates carbon tetrachloride-induced TGF-β1/Smad3 signaling and liver fibrosis in mice. AU - Fan,Kerui, AU - Wu,Kejia, AU - Lin,Ling, AU - Ge,Pu, AU - Dai,Jie, AU - He,Xiaojiao, AU - Hu,Kai, AU - Zhang,Li, Y1 - 2017/04/05/ PY - 2017/01/19/received PY - 2017/03/24/revised PY - 2017/03/26/accepted PY - 2017/4/9/pubmed PY - 2018/2/22/medline PY - 2017/4/9/entrez KW - Carbon tetrachloride KW - Liver fibrosis KW - Metformin KW - Smad3 KW - Transforming growth factor beta 1 SP - 421 EP - 426 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 90 N2 - Increasing evidence suggests that the widely used antidiabetic drug metformin have an extensive therapeutic range beyond hypoglycemic therapy. We previously found that metformin significantly attenuated acute hepatitis. The present study investigated the potential effects of metformin on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. The results indicated that treatment with metformin suppressed CCl4-induced elevation of liver index, formation of fibrotic septa, accumulation of connective tissue and upregulation of collagen I. These effects were not associated with increase of the antioxidative transcription factor nuclear erythroid 2-related factor 2 (NRF2) or its downstream targets, heme oxygenase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). However, treatment with metformin suppressed CCl4-induced expression of transforming growth factor beta 1 (TGF-β1) and phosphorylation of Smad3, which was accompanied with decreased level of alpha smooth muscle actin (α-SMA), a marker for the activated hepatic stellate cells (HSCs). These data indicates that metformin could mitigate CCl4-induced liver fibrosis and these beneficial effects might result from suppressed TGF-β1/Smad3 signaling. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/28390311/Metformin_mitigates_carbon_tetrachloride_induced_TGF_β1/Smad3_signaling_and_liver_fibrosis_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)30295-0 DB - PRIME DP - Unbound Medicine ER -