ArticleJournal of gastroenterology2014
Dipeptidyl peptidase-4 inhibitor attenuates hepatic fibrosis via suppression of activated hepatic stellate cell in rats.
Article in Journal of gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 130 citations in OpenAlex.
- DPP4 Substrate Supplementation Protects From WNT-Induced Lipid Depletion in Dermal Adipocytes.Experimental dermatology · 2026Article
- Association of DPP4 with esophageal stricture progression and the Hippo-YAP pathway.Animal models and experimental medicine · 2026Article
- Effects of Linagliptin on Liver Enzymes in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.Life (Basel, Switzerland) · 2026Review
- Dipeptidyl peptidase-4 inhibitors suppress myofibroblastic differentiation and hyaluronan synthesis in Graves' orbitopathy fibroblasts.Frontiers in endocrinology · 2026Article
- Gemigliptin Alleviates Succinate Induced Endoplasmic Reticulum Stress and Activation of Hepatic Stellate Cells.Journal of Korean medical science · 2025Article
- Identification and In Vitro Evaluation of Milkfish (Foods (Basel, Switzerland) · 2025Article
- Dual therapy with vildagliptin and sacubitril/valsartan alleviates portal hypertension and inhibits soluble epoxide hydrolase in cirrhotic rats.World journal of gastroenterology · 2025Article
- Metabolic Sparks in the Liver: Metabolic and Epigenetic Reprogramming in Hepatic Stellate Cells Activation and Its Implications for Human Metabolic Diseases.Diabetes & metabolism journal · 2025Review
- The antifibrotic effect of Vildagliptin and Diaminodiphenyl Sulfone in murine schistosomiasis mansoni.Scientific reports · 2025Article
- Beyond glycemic control: the cardiac and hepatic benefits of SGLT2 and DPP-4 inhibitors in mitigating chronic cadmium-induced inflammation, oxidative/nitrative stress, apoptosis and fibrosis.Frontiers in physiology · 2025Article
- Dipeptidyl peptidase IV inhibitors reduce hepatic fibrosis and lipid accumulation in rat intestinal failure-associated liver disease models.Pediatric surgery international · 2024Article
- Article
- Tissue fibrosis associated depletion of lipid-filled cells.Experimental dermatology · 2024Review
- Cafeteria Diet-Induced Obesity Worsens Experimental CKD.Nutrients · 2023Article
- DPP-4 Inhibitors Attenuate Fibrosis After Glaucoma Filtering Surgery by Suppressing the TGF-β/Smad Signaling Pathway.Investigative ophthalmology & visual science · 2023Article
- Importance of Fibrosis in the Pathogenesis of Uterine Leiomyoma and the Promising Anti-fibrotic Effects of Dipeptidyl Peptidase-4 and Fibroblast Activation Protein Inhibitors in the Treatment of Uterine Leiomyoma.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Coronavirus Disease-2019 and Implications on the Liver.Clinics in liver disease · 2023Review
- Hepatocyte-derived DPP4 regulates portal GLP-1 bioactivity, modulates glucose production, and when absent influences NAFLD progression.JCI insight · 2023Article
- Gemigliptin Alleviates Succinate-Induced Hepatic Stellate Cell Activation by Ameliorating Mitochondrial Dysfunction.Endocrinology and metabolism (Seoul, Korea) · 2022Article
- Evogliptin Directly Inhibits Inflammatory and Fibrotic Signaling in Isolated Liver Cells.International journal of molecular sciences · 2022Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDipeptidyl peptidase-4 inhibitor (DPP4-I) is clinically used as a new oral antidiabetic agent. Although DPP4 is reportedly associated with the progression of chronic liver diseases, the effect of DPP4-I on liver fibrosis development is still obscure. This study was designed to elucidate the effect of DPP4-I on liver fibrosis development in conjunction with the activated hepatic stellate cells (Ac-HSCs).
methodsThe antifibrotic effect of DPP4-I was assessed in vivo and in vitro using porcine serum-induced experimental liver fibrosis model. DPP4-I, sitagliptin, at a clinically comparable low dose was administered by gavage daily.
resultsDPP4-I significantly attenuated liver fibrosis development along with the suppression of hepatic transforming growth factor (TGF)-β1, total collagen, and tissue inhibitor of metalloproteinases-1 in a dose-dependent manner. These suppressive effects occurred almost concurrently with the attenuation of HSCs activation. Our in vitro studies showed that DPP4-I inhibited platelet-derived growth factor-BB-mediated proliferation of the Ac-HSCs as well as upregulation of TGF-β1 and α1(I)-procollagen at magnitudes similar to those of the in vivo studies. The inhibitory effects of DPP4-I against HSCs proliferation and fibrogenic gene expression are mediated through the inhibition of the phosphorylation of ERK1/2, p38 and Smad2/3, respectively.
conclusionsDPP4-I markedly inhibits liver fibrosis development in rats via suppression of HSCs proliferation and collagen synthesis. These suppressive effects are associated with dephosphorylation of ERK1/2, p38 and Smad2/3 in the HSCs. Since DPP4-I is widely used in clinical practice, this drug may represent a potential new therapeutic strategy against liver fibrosis in the near future.
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Registered trials
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 OpenQuestion graph.