TGF-β1 inhibits autophagy and collagen degradation in rat bronchial fibroblasts

Abstract

Chronic obstructive pulmonary disease (COPD) is a major global health concern with an increasing prevalence. Notably, autophagy plays a crucial role in the pathophysiology of airway remodeling. However, further research is required to determine the precise mechanism of autophagy in rat bronchial fibroblasts (RBFs). In this study, we investigated the role of transforming growth factor-β1 (TGF-β1) on RBF-related collagen degradation following autophagy. We established rapamycin- and starvation-induced autophagy models of RBFs and then analyzed the expression of autophagy-related proteins (LC3-II, Beclin-1, and P62) in RBFs treated with TGF-β1. We also measured the levels of matrix metalloproteinase-1 (MMP-1) and its inhibitor, matrix metalloproteinase inhibitor-1 (TIMP-1) in the RBF supernatant using an enzyme-linked immunosorbent assay. Our results showed that TGF-β1 promoted RBF growth in a concentration-dependent manner, while rapamycin lowered RBF survival rates. TGF-β1 downregulated LC3-II and Beclin-1 expression but increased P62 expression levels after rapamycin and starvation-induced autophagy in RBFs. Adding TGF-β1 elevated TIMP-1 protein levels and reduced MMP-1 protein levels. The present study showed for the first time that TGF-β1 reduces airway remodeling in RBFs by inhibiting autophagy and collagen degradation, suggesting the potential therapeutic value of TGF-β1 for the prevention and treatment of COPD.