Evidence mapPaperPMID 41327925Full record

ArticleJournal of Korean medical science2025

Gemigliptin Alleviates Succinate Induced Endoplasmic Reticulum Stress and Activation of Hepatic Stellate Cells.

Dinh-Vinh Do, Giang Nguyen, So Young Park, Eun-Hee Cho

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Article in Journal of Korean medical science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Dinh-Vinh DoDepartment of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Korea.ORCID https://orcid.org/0000-0002-2280-1031
Giang NguyenDepartment of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Korea.ORCID https://orcid.org/0000-0001-9269-262X
So Young ParkDepartment of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Korea. psoy0122@gmail.com.ORCID https://orcid.org/0000-0003-1518-2516
Eun-Hee ChoDepartment of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Korea. ehcho@kangwon.ac.kr.ORCID https://orcid.org/0000-0002-1349-8894

Funding

Daewoong PharmaceuticalsKorea government NRF-2016R1C1B2011968
6 · The paper itself

Abstract

backgroundHepatic stellate cells (HSCs) activation is the principal event in the development of liver fibrosis in which succinate-G-protein coupled receptor 91 signaling has recently been shown to be a contributor. Moreover, endoplasmic reticulum (ER) stress has been reported to involve in HSC activation, but its association with succinate in pathogenesis of liver fibrosis remains scarce. In this study, we investigated the role of gemigliptin, an antidiabetic dipeptidyl peptidase-4 inhibitor, in the succinate-induced ER stress and activation of HSCs.

methodsLX-2 cells, the immortalized human HSCs, were treated with succinate and gemigliptin. For animal experiments, C57BL/6N mice were divided into 3 groups: control diet, high-fat high-cholesterol (HFHC) diet, and HFHC diet mixed with gemigliptin.

resultsSuccinate significantly induced HSC activation and increased expression of inflammatory markers and the increase in the migration of HSCs. The treatment of succinate also caused ER dilation and activated the unfolded protein response signaling as protein kinase RNA-like ER kinase, eIF2alpha, binding immunoglobulin protein, suggesting increasing ER stress in HSCs. All responses of HSCs to succinate were attenuated with the co-treatment of gemigliptin. Moreover, the exposure of HSCs to tunicamycin, an inducer of ER stress, promoted the expression of α-smooth muscle actin, proliferation and migration of HSCs. In vivo, the level of fibrotic and ER stress markers was increased in mice fed with HFHC diet and the administration of gemigliptin improved these changes in HFHC-induced mice.

conclusionThis study showed the involvement of ER stress in the activation of succinate-induced LX-2 HSCs and gemigliptin significantly reduced ER stress in HSC activation. Therefore, gemigliptin may become an anti-fibrotic agent and targeting to succinate and ER stress may be a promising therapeutic in the management of liver fibrosis.

Indexed as

Dipeptidyl-Peptidase IV InhibitorsEndoplasmic Reticulum StressHepatic Stellate CellsPiperidonesPyrimidinesSuccinic AcidAnimalsCell LineCell MovementDiet, High-FatEukaryotic Initiation Factor-2HumansLiver CirrhosisMaleMiceMice, Inbred C57BLDipeptidyl-Peptidase IV InhibitorsEukaryotic Initiation Factor-2LC15-0444PiperidonesPyrimidinesSuccinic AcidEndoplasmic Reticulum StressGemigliptinHepatic Stellate CellsLiver CirrhosisSuccinic Acid

Identifiers

PMID41327925
PMCPMC12669632

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.