ArticleFrontiers in pharmacology2020
Soluble Dipeptidyl Peptidase-4 Induces Fibroblast Activation Through Proteinase-Activated Receptor-2.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Protease-Activated Receptor-2 as a Proteolytic Rheostat in Colorectal and Pancreatic Cancer: From Mechanism to Biomarker-Guided Therapy.International journal of molecular sciences · 2026Review
- Assessing the therapeutic effects of DPP4 Inhibitors on TGF-β2-induced Lens Opacity.Experimental eye research · 2026Article
- Keratinocyte self-renewal and differentiation is dictated by extrinsic signals from dermal extracellular matrices.Open biology · 2025Article
- SerpinB3/Protease Activated Receptor-2 Axis Is Essential for SARS CoV-2 Infection.ACS infectious diseases · 2025Article
- Elimination of hepatocyte-derived DPP4 downregulates cardiac immune- and collagen-related genes but does not alter cardiac function in aged male mice.Physiological reports · 2025Article
- Dipeptidyl peptidase 4 as an injury-responsive protein in the mouse sciatic nerve.Molecules and cells · 2024Article
- New Insights into the Pleiotropic Actions of Dipeptidyl Peptidase-4 Inhibitors Beyond Glycaemic Control.TouchREVIEWS in endocrinology · 2024Review
- Potential Role of Dipeptidyl Peptidase-4 in Regulating Mitochondria and Oxidative Stress in Cardiomyocytes.Cardiovascular toxicology · 2024Article
- Adipocyte hypertrophy associates withiScience · 2024Article
- Protease-Activated Receptor 2 in inflammatory skin disease: current evidence and future perspectives.Frontiers in immunology · 2024Review
- Revolutionizing Treatment Strategies for Autoimmune and Inflammatory Disorders: The Impact of Dipeptidyl-Peptidase 4 Inhibitors.Journal of inflammation research · 2024Review
- Soluble dipeptidyl peptidase-4 induces epithelial-mesenchymal transition through tumor growth factor-β receptor.Pharmacological reports : PR · 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
- Non-canonical function of DPP4 promotes cognitive impairment through ERp29-associated mitochondrial calcium overload in diabetes.iScience · 2023Article
- Potential Effect of DPP-4 Inhibitors Towards Hepatic Diseases and Associated Glucose Intolerance.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Review
- Emerging Role of Dipeptidyl Peptidase-4 in Autoimmune Disease.Frontiers in immunology · 2022 · on this mapReview
- Stimulation of Synthesis and Lysis of Extracellular Matrix Proteins in Fibrosis Associated with Lymphedema.Dermatopathology (Basel, Switzerland) · 2021Article
- Phagocytosis by stroma confounds coculture studies.iScience · 2021Article
- The effect of dipeptidyl peptidase IV on disease-associated microglia phenotypic transformation in epilepsy.Journal of neuroinflammation · 2021Article
- The Roles of Dipeptidyl Peptidase 4 (DPP4) and DPP4 Inhibitors in Different Lung Diseases: New Evidence.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblasts are the chief secretory cells of the extracellular matrix (ECM) responsible for basal deposition and degradation of the ECM under normal conditions. During stress, fibroblasts undergo continuous activation, which is defined as the differentiation of fibroblasts into myofibroblasts, a cell type with an elevated capacity for secreting ECM proteins. Dipeptidyl peptidase-4 (DPP4) is a ubiquitously expressed transmembrane glycoprotein and exerts effects that are both dependent and independent of its enzymatic activity. DPP4 has been demonstrated to define fibroblast populations in human skin biopsies of systemic sclerosis. Shedding of DPP4 from different tissues into the circulation appears to be involved in the pathogenesis of the diseases. The mechanism underlying soluble DPP4-induced dermal fibrosis has not been clearly determined. The effects of DPP4 on murine 3T3 fibroblasts and human dermal fibroblasts were evaluated by measuring the expression of fibrotic proteins, such as α-SMA and collagen. Soluble DPP4 stimulated the activation of fibroblasts in a dose-dependent manner by activating nuclear factor-kappa B (NF-κB) and suppressor of mothers against decapentaplegic (SMAD) signaling. Blocking proteinase-activated receptor-2 (PAR2) abrogated the DPP4-induced activation of NF-κB and SMAD and expression of fibrosis-associated proteins in fibroblasts. Linagliptin, a clinically available DPP4 inhibitor, was observed to abrogate the soluble DPP4-induced expression of fibrotic proteins. This study demonstrated the mechanism underlying soluble DPP4, which activated NF-κB and SMAD signaling through PAR2, leading to fibroblast activation. Our data extend the current view of soluble DPP4. Elevated levels of circulating soluble DPP4 may contribute to one of the mediators that induce dermal fibrosis in patients.
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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 OpenQuestion graph.