2. Academic Validation
  3. Alogliptin alleviates liver fibrosis via suppression of activated hepatic stellate cell

Alogliptin alleviates liver fibrosis via suppression of activated hepatic stellate cell

  • Biochem Biophys Res Commun. 2019 Apr 2;511(2):387-393. doi: 10.1016/j.bbrc.2019.02.065.
Hanyan Zhang 1,  Dandan Sun 2,  Guanzhen Wang 3,  Shichao Cui 4,  Robert A Field 5,  Jia Li 6,  Yi Zang 7
Affiliations

Affiliations

  • 1 School of Pharmacy, Nanchang University, 461 Bayi Road, Nanchang, 330006, China. Electronic address: zhanghanyan@simm.ac.cn.
  • 2 National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: ddsun@simm.ac.cn.
  • 3 National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: wgz290302648@simm.ac.cn.
  • 4 National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: sccui@simm.ac.cn.
  • 5 Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK. Electronic address: rob.field@jic.ac.uk.
  • 6 National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: jli@simm.ac.cn.
  • 7 National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: yzang@simm.ac.cn.
PMID: 30797555 DOI: 10.1016/j.bbrc.2019.02.065
Abstract

Liver fibrosis occurs in most types of chronic liver diseases. The understanding of the pathogenesis of liver fibrosis has grown considerably, but the effective treatments are still lacking. Alogliptin, a classical Dipeptidyl peptidase-4 (DPP4) inhibitor with great effects on type 2 diabetes, has shown the potential to protect liver, but its effects on the progression of liver fibrosis have not been clarified. Herein, we explored the anti-fibrosis effects of alogliptin. In vitro, we demonstrated that alogliptin suppressed the activation of LX-2 upon Transforming Growth Factor-β (TGF-β) challenge. In vivo, chronic treatment with alogliptin alleviated hepatic steatosis and protected from the liver injury in ob/ob mice, which delayed the progression of liver fibrosis. Furthermore, alogliptin significantly relieved the hepatic fibrosis in CCl4-induced liver fibrosis mouse model. In conclusion, our results demonstrate that negatively modulation of alogliptin on hepatic stellate cell (HSC) activation might contribute to liver fibrosis alleviation. Our research provides the potential possibility of alogliptin on the application for liver fibrosis therapy and suggests that DPP4 may be a novel target for liver fibrosis therapy.

Keywords

Alogliptin; DPP4; Hepatic stellate cell; Liver fibrosis.

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