The role of autophagy in idiopathic pulmonary fibrosis: from mechanisms to therapies

Abstract

Idiopathic pulmonary fibrosis (IPF) is an interstitial pulmonary disease with an extremely poor prognosis. Autophagy is a fundamental intracellular process involved in maintaining cellular homeostasis and regulating cell survival. Autophagy deficiency has been shown to play an important role in the progression of pulmonary fibrosis. This review focused on the six steps of autophagy, as well as the interplay between autophagy and other seven pulmonary fibrosis related mechanisms, which include extracellular matrix deposition, myofibroblast differentiation, epithelial–mesenchymal transition, pulmonary epithelial cell dysfunction, apoptosis, TGF-β1 pathway, and the renin-angiotensin system. In addition, this review also summarized autophagy-related signaling pathways such as mTOR, MAPK, JAK2/STAT3 signaling, p65, and Keap1/Nrf2 signaling during the development of IPF. Furthermore, this review also illustrated the commonly used autophagy detection methods, the currently approved antifibrotic drugs pirfenidone and nintedanib, and several prospective compounds targeting autophagy for the treatment of IPF.