[논문]PDGF Promotes the Warburg Effect in Pulmonary Arterial Smooth Muscle Cells via Activation of the PI3K/AKT/mTOR/HIF-1α Signaling Pathway

Xiao, Yunbin; Peng, Hongyan; Hong, Chenliang; Chen, Zhi; Deng, Xicheng; Wang, Aiping; Yang, Fang; Yang, Li; Chen, Chen; Qin, Xuping

doi:10.1159/000479401

PDGF Promotes the Warburg Effect in Pulmonary Arterial Smooth Muscle Cells via Activation of the PI3K/AKT/mTOR/HIF-1α Signaling Pathway 원문보기

Cellular physiology and biochemistry, v.42 no.4, 2017년, pp.1603 - 1613

Xiao, Yunbin (Academy of Pediatrics, University of South China, Hengyang, China) , Peng, Hongyan (Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China) , Hong, Chenliang (Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China) , Chen, Zhi (Department of Cardiology, Hunan Children&apos) , Deng, Xicheng (s Hospital, Changsha, China) , Wang, Aiping (Department of Cardiology, Hunan Children&apos) , Yang, Fang (s Hospital, Changsha, China) , Yang, Li (Department of Anatomy, School of Medicine, University of South China, Hengyang, China) , Chen, Chen (Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China) , Qin, Xuping (Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China)

Abstract ▼ AI-Helper

AbstractBackground/Aims: The enhanced proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a central pathological component in pulmonary arterial hypertension (PAH). Both the Warburg effect and platelet-derived growth factor (PDGF) are involved in the proliferation of PASMCs. However, the mechanism underlying the crosstalk between the Warburg effect and PDGF during PASMC proliferation is still unknown. We hypothesized that PDGF promotes the Warburg effect via activating the phosphatidylinositol 3-kinase (PI3K) signaling pathway and hypoxia-inducible factor 1-α (HIF-1α) in proliferative PASMCs. Methods: PASMCs were derived from pulmonary arteries of SD rats; cell viability, the presence of metabolites, and metabolic enzyme activities assay were determined by MTT assays, kit assays and western blot analysis, respectively. Results: PDGF promoted PASMC proliferation in a dose- and time-dependent manner, accompanied by an enhanced Warburg effect. Treatment with PDGFR antagonists, Warburg effect inhibitor and PDK1 inhibitor significantly inhibited PI3K signaling activation, HIF-1α expression and PASMC proliferation induced by PDGF, respectively. Furthermore, treatment with PI3K signaling pathway inhibitors remarkably suppressed PDGF-induced PASMC proliferation and the Warburg effect. Conclusion: microplate reader (Biotek, Winooski The Warburg effect plays a critical role in PDGF-induced PASMC proliferation and is mediated by activation of the PI3K signaling pathway and HIF-1α.

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참고문헌 (27)

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PDGF Promotes the Warburg Effect in Pulmonary Arterial Smooth Muscle Cells via Activation of the PI3K/AKT/mTOR/HIF-1α Signaling Pathway 원문보기

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