Mir-206 regulates pulmonary artery smooth muscle cell proliferation and differentiation.
Pulmonary Arterial Hypertension (PAH) is a progressive devastating disease characterized by excessive proliferation of the Pulmonary Arterial Smooth Muscle Cells (PASMCs). Studies suggest that PAH and cancers share an apoptosis-resistant state featuring excessive cell proliferation. MicroRNA-206 (miR-206) is known to regulate proliferation and is implicated in various types of cancers. However, the role of miR-206 in PAH has not been studied. In this study, it is hypothesized that miR-206 could play a role in the proliferation of PASMCs. In the present study, the expression patterns of miR-206 were investigated in normal and hypertensive mouse PASMCs. The effects of miR-206 in modulating cell proliferation, apoptosis and smooth muscle cell markers in human pulmonary artery smooth muscle cells (hPASMCs) were investigated in vitro. miR-206 expression in mouse PASMCs was correlated with an increase in right ventricular systolic pressure. Reduction of miR-206 levels in hPASMCs causes increased proliferation and reduced apoptosis and these effects were reversed by the overexpression of miR-206. miR-206 over expression also increased the levels of smooth muscle cell differentiation markers α-smooth muscle actin and calponin implicating its importance in the differentiation of SMCs. miR-206 overexpression down regulated Notch-3 expression, which is key a factor in PAH development. These results suggest that miR-206 is a potential regulator of proliferation, apoptosis and differentiation of PASMCs, and that it could be used as a novel treatment strategy in PAH.
Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, FL, USA.
Samuel
S
Jalali
Gurukumar K
GK
Ramanathan
Prasanna Tamarapu
PT
Parthasarathy
Salman
S
Aljubran
Lakshmi
L
Galam
Asfiya
A
Yunus
Sara
S
Garcia
Ruan R
RR
Cox
Richard F
RF
Lockey
Narasaiah
N
Kolliputi
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C546087:MIRN206 microRNA, human; D035683:MicroRNAs; C540669:Mirn206 microRNA, mouse; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch