JAK2 mediates lung fibrosis, pulmonary vascular remodelling and hypertension in idiopathic pulmonary fibrosis: an experimental study
- 10 February 2018
- Vol. 73 (6), 519-529
- https://doi.org/10.1136/thoraxjnl-2017-210728
Abstract
Background Pulmonary hypertension (PH) is a common disorder in patients with idiopathic pulmonary fibrosis (IPF) and portends a poor prognosis. Recent studies using vasodilators approved for PH have failed in improving IPF mainly due to ventilation (V)/perfusion (Q) mismatching and oxygen desaturation. Janus kinase type 2 (JAK2) is a non-receptor tyrosine kinase activated by a broad spectrum of profibrotic and vasoactive mediators, but its role in PH associated to PH is unknown. Objective The study of JAK2 as potential target to treat PH in IPF. Methods and results JAK2 expression was increased in pulmonary arteries (PAs) from IPF (n=10; 1.93-fold; P=0.0011) and IPF+PH (n=9; 2.65-fold; PCa). JAK2 inhibition activated BKCa channels and reduced intracellular Ca2+. JSI-124 1 mg/kg/day, reduced bleomycin-induced lung fibrosis, PA remodelling, right ventricular hypertrophy, PA hypertension and V/Q mismatching in rats. The animal studies followed the ARRIVE guidelines. Conclusions JAK2 participates in PA remodelling and tension and may be an attractive target to treat IPF associated to PH.Funding Information
- Consejo Superior de Investigaciones Científicas
- Generalitat Valenciana
- centro de investigaciones biomédicas en red de enfermedades respiratorias
- Instituto de Salud Carlos III
- Secretaría de Estado de Investigación, Desarrollo e Innovación
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