Bingbing Ye, Danyan Su, Yuqin Huang, Dongli Liu, Yanyun Huang, Suyuan Qin, Cheng Chen, Yusheng Pang
First Affiliated Hospital of Guangxi Medical University.
China
Clinical and Experimental Hypertension
Clin Exp Hypertens 2025; 47:
DOI: 10.1080/10641963.2025.2583193
Abstract
This study was designed to elucidate the role of circPcmtd1 in regulating pulmonary artery smooth muscle cells (PASMCs) proliferation and migration, through the HSP90AB1/AKT signaling axis, in rats with high pulmonary blood flow-induced PAH. A rat model of high pulmonary blood flow-induced PAH was established by an abdominal aorta-inferior vena cava shunt surgery. The expression of circPcmtd1 in PASMCs of rats with high pulmonary blood flow-induced PAH was verified by qRT-PCR. The effects of circPcmtd1 on the proliferation and migration of PASMCs were explored by lentiviral transfection, cell proliferation assay, and scratch assay. RNA pull-down assay, mass spectrometric analysis, lentiviral transfection, and western blot were used to explore the molecular mechanisms by which circPcmtd1 regulated the proliferation and migration of PASMCs in rats with high pulmonary blood flow-induced PAH. We found that the expression of circPcmtd1 was down-regulated in PASMCs of rats with high pulmonary blood flow-induced PAH. Functional experiments showed that overexpression of circPcmtd1 inhibited the proliferation and migration of PASMCs. RNA pull-down assay and mass spectrometric analysis revealed that circPcmtd1 could bind to HSP90AB1 protein. Further, we found that high expression of HSP90AB1 could promote the proliferation and migration of PASMCs in rats with high pulmonary blood flow-induced PAH. Mechanistic investigation demonstrated that the binding of circPcmtd1 to HSP90AB1 could regulate the phosphorylation of AKT. In conclusion, circPcmtd1 directly bound to the HSP90AB1 protein to mediate the phosphorylation of AKT, thereby regulating the proliferation and migration of PASMCs.
Category
Class I. Pulmonary Hypertension Associated with Congenital Cardiovascular Disease
Animal Models of Pulmonary Vascular Disease and Therapy
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
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Free PDF File or Full Text Article Available Through PubMed or DOI: Yes