[HTML][HTML] IL-11 system participates in pulmonary artery remodeling and hypertension in pulmonary fibrosis
J Milara, I Roger, P Montero, E Artigues, J Escrivá… - Respiratory …, 2022 - Springer
J Milara, I Roger, P Montero, E Artigues, J Escrivá, J Cortijo
Respiratory research, 2022•SpringerBackground Pulmonary hypertension (PH) associated to idiopathic pulmonary fibrosis (IPF)
portends a poor prognosis. IL-11 has been implicated in fibrotic diseases, but their role on
pulmonary vessels is unknown. Here we analyzed the contribution of IL-11 to PH in patients
with IPF and the potential mechanism implicated. Methods Pulmonary arteries, lung tissue
and serum of control subjects (n= 20), IPF (n= 20) and PH associated to IPF (n= 20) were
used to study the expression and localization of IL-11 and IL-11Rα. Two models of IL-11 and …
portends a poor prognosis. IL-11 has been implicated in fibrotic diseases, but their role on
pulmonary vessels is unknown. Here we analyzed the contribution of IL-11 to PH in patients
with IPF and the potential mechanism implicated. Methods Pulmonary arteries, lung tissue
and serum of control subjects (n= 20), IPF (n= 20) and PH associated to IPF (n= 20) were
used to study the expression and localization of IL-11 and IL-11Rα. Two models of IL-11 and …
Background
Pulmonary hypertension (PH) associated to idiopathic pulmonary fibrosis (IPF) portends a poor prognosis. IL-11 has been implicated in fibrotic diseases, but their role on pulmonary vessels is unknown. Here we analyzed the contribution of IL-11 to PH in patients with IPF and the potential mechanism implicated.
Methods
Pulmonary arteries, lung tissue and serum of control subjects (n = 20), IPF (n = 20) and PH associated to IPF (n = 20) were used to study the expression and localization of IL-11 and IL-11Rα. Two models of IL-11 and bleomycin-induced lung fibrosis associated to PH were used in Tie2-GFP transgenic mice to evaluate the contribution of IL-11 and endothelial cells to pulmonary artery remodeling. The effect of IL-11 and soluble IL-11Rα on human pulmonary artery endothelial cells and smooth muscle cell transformations and proliferation were analyzed.
Results
IL-11 and IL-11Rα were over-expressed in pulmonary arteries and serum of patients with PH associated to IPF vs IPF patients without PH. Recombinant mice (rm)IL-11 induced lung fibrosis and PH in Tie2-GFP mice, activating in vivo EnMT as a contributor of pulmonary artery remodeling and lung fibrosis. Transient transfection of siRNA-IL-11 reduced lung fibrosis and PH in Tie2-GFP bleomycin model. Human (h)rIL-11 and soluble hrIL-11Rα induced endothelial to mesenchymal transition (EnMT) and pulmonary artery smooth muscle cell to myofibroblast-like transformation, cell proliferation and senescence in vitro.
Conclusions
IL-11 and IL-11Rα are overexpressed in pulmonary arteries of PH associated to IPF patients, and contributes to pulmonary artery remodeling and PH.
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