Microrna-26b attenuates monocrotaline-induced pulmonary vascular remodeling via targeting connective tissue growth factor (CTGF) and cyclin D1 (CCND1).
MicroRNAs are involved in the control of cell growth, and deregulated pulmonary artery smooth muscle cell proliferation plays an essential role in the development of pulmonary hypertension. The objective of this study was to identify differentially expressed microRNA(s) and explore its therapeutic role in treatment of the disease. MicroRNA expression profile analysis showed microRNA-26b was differentially expressed in pulmonary artery smooth muscle cells harvested from monocrotaline-treated rats, and we validated microRNA-26b targets, in vitro and in vivo, CTGF and CCND1, both of which have been shown, in our previous work, to be involved in the pathogenesis of pulmonary hypertension. In vivo experiments demonstrated monocrotaline-induced pulmonary artery remodeling could be almost completely abolished by administration of microRNA-26b, while CTGF or CCND1 shRNA significantly, but only partially, attenuated the remodeling by silencing the designed target. Additionally, exogenous expression of the microRNA-26b substantially downregulated CTGF and CCND1 in human pulmonary artery smooth muscle cells. MicroRNA-26b might be a potent therapeutic tool to treat pulmonary hypertension.
Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Ran
R
Wang
Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Xing
X
Ding
Department of Occupational Diseases, Hefei Third Clinical College, Anhui Medical University, Hefei 230001, China.
Sijing
S
Zhou
Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Min
M
Li
Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Li
L
Sun
Division of Pulmonary/Critical Care Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA.
Xuan
X
Xu
Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Guanghe
G
Fei
D020413:3' Untranslated Regions; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D016686:Monocrotaline / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D066253:Vascular Remodeling / Q000187:drug effects* / Q000235:genetics*
D020413:3' Untranslated Regions; C556274:MIRN26 microRNA, rat; D035683:MicroRNAs; D034741:RNA, Small Interfering; D019938:Cyclin D1; D055513:Connective Tissue Growth Factor; D016686:Monocrotaline
CTGF; cyclin D1; miR-26b; monocrotaline; pulmonary hypertension