UC-MSCs prevent cigarette smoke-induced early cellular senescence like phenotype in bronchial epithelial cells via the SIRT1/PGC-1α pathway

Chronic obstructive pulmonary disease (COPD) is an age-related chronic disease, and most of the patients are elderly. Smoking is the main pathogenic factor, and the course of disease continues to develop. Cigarette smoke exposure leads to mitochondrial dysfunction and activation of cellular senescence. Umbilical cord mesenchymal stem cells (UC-MSCs) play a significant role in mitochondrial protection, airway repair and tissue regeneration.SIRT1/PGC-1α is a key regulator of mitochondrial function and cellular senescence. Therefore, this study aims to explore whether UC-MSCs can improve cigarette smoke extract (CSE)-induced mitochondrial dysfunction and cellular senescence in bronchial epithelial cells by activating the SIRT1/PGC-1α pathway. In vitro results show that: (1) CSE induced mitochondrial dynamic imbalance, leading to mitochondrial dysfunction and ROS accumulation, which induced cellular senescence. (2) UC-MSCs activate the SIRT1/PGC-1α pathway and significantly reduce the expression of markers related to cellular senescence and improving mitochondrial function after CSE induction. (3) The SIRT1 inhibitor EX527 reversed the protective effect of UC-MSCs. This study, for the first time, reveals that UC-MSCs can improve CSE-induced mitochondrial dysfunction and cellular senescence in bronchial epithelial cells by activating the SIRT1/PGC-1α pathway. It provides a new target for COPD treatment and a strategy for slowing the progression of the disease.