Endothelial cells in pulmonary fibrosis: more than a bystander

Pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF), is a debilitating and often fatal lung disorder characterised by the abnormal accumulation of extracellular matrix (ECM), leading to fibrotic scarring and lung stiffening [1]. Although the exact mechanism is yet to be fully understood, aberrant tissue remodelling with excess ECM is a critical factor in the progression of pulmonary fibrosis [1, 2]. Myofibroblasts are specialised fibroblasts that express α-smooth muscle actin (α-SMA) and can exert contractile forces, in addition to their involvement in production of pathological ECM components, including fibrillar collagens I and III, and fibronectin [3]. This excessive fibrotic ECM deposition results in increased stiffness, which further activates transforming growth factor (TGF)-β from a latent form and stimulates myofibroblast differentiation and production of profibrotic mediators, such as connective tissue growth factor, thus perpetuating a vicious cycle of fibrosis [3, 4]. Focusing on EndMT, Wu et al. discovered that EC-like myofibroblasts are able to differentiate into myofibroblasts, resulting in a significant contribution to the pathogenesis of pulmonary fibrosis, and this process is redirected through induction of FoxA2 https://bit.ly/3YQvSIX