Preliminary Mechanism of Glial Maturation Factor β on Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

Abstract

AbstractRecent evidence suggests that glia maturation factor β (GMFβ) is important in the pathogenesis of pulmonary arterial hpertension (PAH), but the underlying mechanism is unknown. To clarify whether GMFβ can be involved in pulmonary vascular remodeling and to explore the role of the IL‐6‐STAT3 pathway in this process, the expression of GMFβ in PAH rats is examined and the expression of downstream molecules including periostin (POSTN) and interleukin‐6 (IL‐6) is measured using real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blot analysis. The location and expression of POSTN is also tested in PAH rats using immunofluorescence. It is proved that GMFβ is upregulated in the lungs of PAH rats. Knockout GMFβ alleviated the MCT‐PAH by reducing right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and pulmonary vascular remodeling. Moreover, the inflammation of the pulmonary vasculature is ameliorated in PAH rats with GMFβ absent. In addition, the IL‐6‐STAT3 signaling pathway is activated in PAH; knockout GMFβ reduced POSTN and IL‐6 production by inhibiting the IL‐6‐STAT3 signaling pathway. Taken together, these findings suggest that knockout GMFβ ameliorates PAH in rats by inhibiting the IL‐6‐STAT3 signaling pathway.