MiR‐21 plays a Role in Smooth Muscle Cell Proliferation induced by Hypoxia

Abstract

Chronic hypoxia is an important contributing factor to the development of pulmonary hypertension. Hypoxia triggers pulmonary vascular smooth muscle cell (PVSMC) remodeling from a differentiated state to a proliferative, dedifferentiated state. cGMP‐dependent protein kinase type 1 (Prkg1) is involved in the regulation of vasomotor tone and remodelling. MicroRNAs play important roles in various biologic processes in cells, where they regulate apoptosis, proliferation, differentiation, development & metabolism. However, the role of microRNAs in hypoxia‐mediated Prkg1 down‐regulation in smooth muscle cells and SMC proliferation is unknown. The objective of the study was to characterize miRNA regulation in PVSMC response to hypoxia, affecting cell proliferation. This is important in understanding the molecular mechanisms triggered by cell exposure to low oxygen tension in Persistent Pulmonary Hypertension (PPH) in neonates. We used human PVSMCs as an in vitro model system and studied the effects of hypoxic (3% oxygen) exposure. Cells were processed for mRNA, protein and microRNA studies. We found reduced mRNA and protein expression of SMC markers such as α‐Smooth muscle actin and calponin as well as Prkg1. Quantitative PCR analyses showed that 24h hypoxia treatment induced miR‐21 upregulation. Our studies suggest that miR‐21 plays a role in hypoxia‐induced smooth muscle cell proliferation. This work was supported by R01 HL075187‐05A1