miR-205-5p accelerates lung fibroblast senescence in IPF patients via mediation of mitochondrial dynamics

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease that occurs primarily in the elderly. Although senescence of lung fibroblasts (LFs) contributes to IPF development, the potential mechanisms underlying LF senescence are not fully understood. This study aimed to delineate the role and underlying mechanisms of miR-205-5p in regulating LF senescence in patients with IPF. The LFs from IPF patients (IPF-LFs) and age-matched controls (Control-LFs) were isolated and cultured. Senescence of LFs was determined by senescence-associated β-galactosidase (SA-β-gal) staining. Mitochondrial morphology of LFs was evaluated by MitoTracker staining and transmission electron microscope. The expression of miR-205-5p was examined by RT-PCR. Compared with Control-LFs, IPF-LFs exhibited increased cellular senescence with higher expression of SA-β-gal, p21 and p16 as well as decreased proliferative capacity. Importantly, IPF-LFs had decreased mitochondrial fission, evidenced by elongated mitochondria and downregulation of mitochondrial fission regulator 1-like protein (MTFR1L). The expression of miR-205-5p was much higher in IPF-LFs than Control-LFs. Notably, upregulation of miR-205-5p in Control-LFs led to increased cellular senescence, whereas downregulation rescued IPF-LF senescence. Mechanistically, miR-205-5p downregulated mitochondrial fission in LFs via MTFR1L, leading to mitochondrial dysfunction and cellular senescence. Taken together, our study illustrated that miR-205-5p serves as a critical regulator of cellular senescence of LFs isolated from IPF patients via mediation of mitochondrial dynamics.