Liraglutide protects high-glucose-stimulated fibroblasts by activating the CD36-JNK-AP1 pathway to downregulate P4HA1 - 18/09/19
, Qinghua Lu a, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
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| pages | 11 |
| Iconographies | 8 |
| Vidéos | 0 |
| Autres | 0 |
Highlights |
• | Glucose promotes proliferation and fibrosis of CFs. |
• | GLP-1 inhibits the biological process of HG-stimulated CFs. |
• | Silencing of P4HA1 suppresses HG-stimulated CFs. |
• | GLP-1 inhibition of P4HA1 is mediated by the CD36-JNK-AP1 pathway. |
Abstract |
Background |
Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus. It’s known that glucagon-like peptide-1 (GLP-1) and prolyl 4-hydroxylase subunit alpha-1 (P4HA1) have significant effect on cardiovascular function, but their interaction in cardiac fibroblasts (CFs) is still being unraveled.
Methods and results |
The present study demonstrated that glucose promotes CFs proliferation and cardiac fibrosis. Using qRT-PCR, Western blot, CCK-8, EdU, flow cytometry, wound healing and Transwell assays to explore the functions of liraglutide and P4HA1 in high-glucose (HG)-induced CFs, we proved that liraglutide as well as silencing of P4HA1 inhibited cell proliferation, migration and invasion, and promoted cell cycle arrest and apoptosis in HG-induced CFs. In addition, liraglutide downregulated P4HA1 expression, upregulated CD36 and P-JNK expression levels, and enhanced the DNA binding activity of AP-1 on P4HA1. Inhibition of CD36 or p--JNK promoted P4HA1 expression.
Conclusions |
Liraglutide may down-regulate P4HA1 expression at least partly though CD36-JNK-AP1 pathway, thereby reducing myocardial fibrosis. Therefore, our study provides novel insight into the molecular mechanism and function of liraglutide in HG-mediated CFs.
Le texte complet de cet article est disponible en PDF.Abbreviations : DCM, GLP-1, P4HA1, CFs, GPCR, MMPs, HG, AP-1, JNK, NC, qRT-PCR, COL I, COL III, CCK8, EdU, IF, EMSA
Keywords : Diabetes, Glucagon-like peptide-1, Prolyl 4-hydroxylases, Activator protein-1, Fibroblast
Plan
Vol 118
Article 109224- octobre 2019 Retour au numéro
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