TY - JOUR
T1 - PPARγ activation inhibits PDGF-induced pulmonary artery smooth muscle cell proliferation and migration by modulating TERT
AU - Zhang, Qianqian
AU - Feng, Wei
AU - Wang, Qingting
AU - Wang, Jian
AU - Chai, Limin
AU - Chen, Yuqian
AU - Wang, Yan
AU - Liu, Jin
AU - Li, Manxiang
AU - Xie, Xinming
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - Cell proliferation
KW - Peroxisome proliferator-activated receptor γ
KW - Pulmonary artery hypertension
KW - Telomerase
KW - Telomerase reverse transcriptase
UR - https://www.scopus.com/pages/publications/85131690685
U2 - 10.1016/j.biopha.2022.113233
DO - 10.1016/j.biopha.2022.113233
M3 - 文章
C2 - 35689861
AN - SCOPUS:85131690685
SN - 0753-3322
VL - 152
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 113233
ER -