MiR-122-5p as a potential regulator of pulmonary vascular wall cell in idiopathic pulmonary arterial hypertension
Hui Zhao,
Ruowang Duan,
Qian Wang,
Xiaoyi Hu,
Qinhua Zhao,
Wenhui Wu,
Rong Jiang,
Sugang Gong,
Lan Wang,
Jinming Liu,
Jie Deng,
Huazheng Liang,
Yuqing Miao,
Ping Yuan
Affiliations
Hui Zhao
School of Materials and Chemistry & Institute of Bismuth and Rhenium, University of Shanghai for Science and Technology, Shanghai 200093, China; Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
Ruowang Duan
Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
Qian Wang
School of Materials and Chemistry & Institute of Bismuth and Rhenium, University of Shanghai for Science and Technology, Shanghai 200093, China; Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
Xiaoyi Hu
Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
Qinhua Zhao
Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
Wenhui Wu
Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
Rong Jiang
Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
Sugang Gong
Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
Lan Wang
Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
Jinming Liu
Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
Jie Deng
Southern Medical University, Guangzhou, 510000, China
Huazheng Liang
Monash Suzhou Research Institute, Suzhou, Jiangsu Province, 215125, China; Corresponding author.
Yuqing Miao
School of Materials and Chemistry & Institute of Bismuth and Rhenium, University of Shanghai for Science and Technology, Shanghai 200093, China; Corresponding author.
Ping Yuan
Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China; Corresponding author.
MicroRNAs (miRNAs) are versatile regulators of pulmonary arterial remodeling in idiopathic pulmonary arterial hypertension (IPAH). We herein aimed to characterize miRNAs in peripheral blood mononuclear cell (PBMC) and plasma exosomes, and investigate specific miRNA expression in pulmonary artery cells and lung tissues in IPAH. A co-dysregulated miRNA was identified from the miRNA expression profiles of PBMC and plasma exosomes in IPAH. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the potential function of differentially expressed miRNAs. Real-time quantitative reverse transcription polymerase chain reaction was used to validate the expression of specific miRNAs in hypoxia-induced pulmonary microvascular endothelial cells (PMECs), pulmonary artery smooth muscle cells (PASMCs), pericyte cells (PCs), and lung tissues of patients with IPAH and rats. Finally, the miRNA-mRNA mechanisms of miR-122-5p were predicted. MiR-122-5p was the only co-upregulated miRNA in PBMC and plasma exosomes in patients with IPAH. Functional analysis of differentially expressed miRNAs revealed associations with the GO terms “transcription, DNA-templated,” “cytoplasm,” and “metal ion binding” in both PBMC and plasma exosomes, KEGG pathway MAPK signaling in PBMC, and KEGG-pathway human papillomavirus infection in plasma exosomes. Hypoxic PMECs and PCs, lung tissue of patients with IPAH, and rats showed increased expression of miR-122-5p, but hypoxic PASMCs showed decreased expression. And miR-122-5p mimics and inhibitor affected cell proliferation. Finally, miR-122-5p was found to potentially target DLAT (in lung tissue) and RIMS1 (in PMECs) in IPAH. According to the dual-luciferase assay, miR-122-5p bound to DLAT or RIMS1. In studies, DLAT imbalance was associated with cell proliferation and migration, RIMS1 is differentially expressed in cancer and correlated with cancer prognosis. Our findings suggest that the miR-122-5p is involved in various biological functions in the adjacent vascular wall cells in IPAH.
