Abstract
Pro-inflammatory cytokines-induced airway remodeling was a significant feature of asthma disease. The aim of the present study was to explore the functional significance of miR-874 in tumor necrosis factor (TNF)-α-treated human fetal airway smooth muscle (fASM) cells. Here, we found that TNF-α treatment significantly down-regulated the expression of miR-874 in fASM cells. MiR-874 overexpression markedly inhibited cell viability and migration, suppressed the expression of PCNA and Ki67, reduced the expression of collagen I and collagen III, decreased the expression and activity of matrix metalloproteinase (MMP)-9 and MMP-2, and induced an obvious elevation of tissue inhibitors of metalloproteinases (TIMPs). In addition, the increased production of interleukin (IL)-6, IL-8 and eotaxin induced by TNF-α were significantly inhibited by miR-874 overexpression. Signal transducers and activators of transcription (STAT) 3 was identified as a direct target of miR-874, and STAT3 overexpression partly reversed the protective effects of miR-874 against TNF-α-induced airway remodeling. Overall, these findings demonstrate that miR-874 inhibits TNF-α-induced remodeling in human fASM cells at least in part by targeting STAT3.