Open AccessJANEX-1 improves acute pulmonary embolism through VEGF and FAK in pulmonary artery smooth muscle cells
Author(s) -
Longfei Pan,
Zhuo Peng,
Rui-peng Zhang,
Rui Zhang,
Dan Liang,
Heming Chen,
Hui Tian
Publication year - 2020
Publication title -
experimental biology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 146
eISSN - 1535-3702
pISSN - 1535-3699
DOI - 10.1177/1535370220942474
Subject(s) - janus kinase , medicine , janus kinase 2 , pulmonary artery , platelet derived growth factor receptor , cancer research , pulmonary hypertension , vascular smooth muscle , pulmonary embolism , growth factor , smooth muscle , receptor
Accumulating evidence suggests that vascular remodeling due to immoderate proliferation and migration of SMCs is a common process occurring in APE. In this work, we tried to find a breakthrough in the pathological mechanism to alleviate the prognosis of APE by improving SMCs proliferation and explored the effect of JANEX-1 on PDGF-induced proliferation-related molecules in PVSMCs and assessed the therapeutic potential of JAK3 for vascular remodeling in APE mice. We demonstrated that JANEX-1, blocking JAK3 expression or activity, reduced JAK3/STAT3 signaling pathway, VEGF expression and FAK activation, and PDGF-induced proliferation of PVSMCs. Moreover, JANEX-1 inhibited the thrombus-induced intimal hyperplasia and the expression of VEGF and FAK activation in neointimal SMCs of APE mice. The data are helpful to elucidate the pharmacological mechanism and potential therapeutic effect of JANEX-1 in APE.