VWF Deficiency Inhibits EndoMT to Attenuate Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, interstitial lung disease lacking efficient drug to reverse it. Thus, to elucidate the complex pathogenesis of IPF and identify new therapeutic targets are urgently needed. It has been revealed that the pathophysiology of IPF is a highly orchestrated process including multiple cell types, where the contribution of endothelial cells (ECs) has also been attracted researchers' attention. However, although the involvement of ECs in fibrosis has been recognized, the underlying key molecules driving these changes are not well-defined. Here, we revealed that von Willebrand factor (VWF), a marker of damaged ECs, and endothelial dysfunction are positively correlated with IPF progression based on reanalysis of gene expression profiles of patients with IPF. Next, we discovered that VWF deficiency attenuated fibrosis in experimental models, including human cell lines (in vitro) and mice (in vivo). Mechanistically, VWF deficiency inhibited endothelial-to-mesenchymal transition (EndoMT), regulated vascular abnormalities and limited M2 macrophage infiltration, which were achieved, at least in part, by the inhibition of Wnt signaling. Our findings provided evidence for the pivotal role of ECs in IPF and revealed VWF might be a driving factor of EndoMT, suggesting that VWF can develop as a potential therapeutic target against IPF. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).