PPARγ activation inhibits PDGF-induced pulmonary artery smooth muscle cell proliferation and migration by modulating TERT - 18/06/22
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Abstract |
Vascular remodeling is a significant feature of pulmonary artery hypertension (PAH), and is characterized by abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Telomerase reverse transcriptase (TERT), as a determining factor for controlling telomerase activity, has been proven to be associated with cell proliferation. This study aims to explore whether TERT mediates the proliferation and migration of PASMCs and the underlying molecular mechanism. Primary PASMCs from Sprague-Dawley (SD) rats were used in this experiment. Cell proliferation and migration were evaluated by Cell Counting Kit-8, EdU incorporation assay and transwell assay, respectively. Telomerase activity was assessed with a rat TE ELISA kit. Small interfering RNA (siRNA) transfection was conducted to silence c-MYC expression. The protein levels of p-Akt, c-MYC, PPARγ and TERT were determined through western blotting. Our work demonstrates that PDGF upregulated TERT expression and telomerase activation by activating Akt and upregulating of c-MYC in PASMCs. Inhibition of Akt with LY294002, knockdown of c-MYC by siRNA or suppression of telomerase activity with BIBR1532 repressed PDGF-induced PASMC proliferation and migration. Furthermore, activation of peroxisome proliferator-activated receptor γ (PPARγ) with pioglitazone suppressed PDGF-induced TERT expression and telomerase activation, leading to inhibition of PASMC proliferation and migration.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Upregulation of TERT mediates PASMCs proliferation and migration. |
• | PDGF promotes PASMCs proliferation and migration via Akt/c-MYC/TERT axis. |
• | PPARγ activation inhibits PASMCs proliferation and migration by regulating TERT expression. |
Abbreviations : PAH, PASMCs, PDGF, TERC, TEP1, TERT, PPARγ, DMEM, FBS, CCK-8, SEM
Keywords : Pulmonary artery hypertension, Telomerase, Telomerase reverse transcriptase, Peroxisome proliferator-activated receptor γ, Cell proliferation
Plan
Vol 152
Article 113233- août 2022 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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