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PDGFBB promotes proliferation and migration via regulating miR-1181/STAT3 axis in human pulmonary arterial smooth muscle cells.
American Journal of Physiology. Lung Cellular and Molecular Physiology 2018 September 14
Platelet-Derived Growth Factor (PDGF) can induce hyperproliferation of Pulmonary Artery Smooth Muscle Cells (PASMCs), which is a key causative factor to the occurrence and progression of pulmonary arterial hypertension (PAH). We previously identified that miR-1181 is significantly downregulated by PDGFBB in human PASMCs. In this work, we further explore the function of miR-1181 and underlying regulatory mechanisms in PDGF-induced PASMCs. First, the expression pattern of miR-1181 was characterized under PDGFBB treatment, and PDGFR/PKCβ signaling was find to repress miR-1181 expression. Then, gain- and loss-of-function experiments were respectively conducted and revealed the prominent role of miR-1181 in inhibiting PASMCs proliferation and migration. Flow cytometry analysis suggested that miR-1181 regulated the PASMCs proliferation through influencing the cell cycle transition from G0/G1 to S phase. Moreover, we exhibited that miR-1181 targeting STAT3 formed a regulatory axis to modulate PASMCs proliferation. Finally, serum miR-1181 expression was also observed to be reduced in adult and newborn PAH patients. Overall, this study provides novel findings that miR-1181/STAT3 axis mediated PDGFBB-induced dysfunction in human PASMCs, implying a potential use of miR-1181 as a therapeutic and diagnostic candidate for the vascular remodeling diseases.
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