CCT6A alleviates pulmonary fibrosis by inhibiting HIF-1α-mediated lactate production

• DOI: 10.1093/jmcb/mjae021
• Publication Date: 2024-05-18T03:56:03Z
• Authors: Peishuo Yan; Kun Yang; Mengwei Xu; Miaomiao Zhu; Yudi Duan; Wenwen Li; Lulu Liu; Chenxi Liang; Zhongzheng Li; Xin Pan; Lan Wang; Guoying Yu
• Keywords: 0301 basic medicine; 03 medical and health sciences; Article

Abstract Idiopathic pulmonary fibrosis (IPF) is a lethal progressive fibrotic lung disease. The development of IPF involves different molecular and cellular processes, recent studies indicate that lactate plays significant role in promoting the progression Nevertheless, mechanism by which metabolism regulated downstream effects remain unclear. chaperone CCT6A performs multiple functions variety biological processes. Our research has identified potential association between serum levels patients. Herein, we found was highly expressed type 2 alveolar epithelial cells (AEC2s) tissues correlated with disease severity. Lactate increases accumulation lipid droplets cells. inhibits synthesis blocking production AEC2s alleviates bleomycin-induced mice. In addition, our results revealed blocks HIF-1α-mediated driving VHL-dependent ubiquitination degradation HIF-1α further lungs. conclusion, propose there pivotal regulatory fibrosis, strategies aimed at targeting these key molecules could represent therapeutic approaches for fibrosis.