The pathological changes of airway smooth muscle (ASM) contribute to airway remodeling during asthma. Here, we investigated the effect of miR-145 on ASM function. We found that miR-145 was aberrantly more highly expressed in ASM cells exposed to cytokine stimulation that mimic the airway conditions of patients with asthma. Repression of miR-145 resulted in decreased ASM cell proliferation and migration in a dose-dependent manner and down-regulation of type I collagen and contractile protein MHC in ASM cells. qRT-PCR and Western blot analysis demonstrated that miR-145 negatively regulated the expression of downstream target Krüppel-like factor 4 (KLF4) protein, and overexpression of KLF4 attenuated the effects of miR-145 on ASM cells. Further studies showed that KLF4 significantly up-regulated the expression of p21 and down-regulated matrix metalloproteinase (MMP-2 and MMP-9). In conclusion, miR-145 overexpression in ASM cells significantly inhibited KLF4, and subsequently affected downstream p21, MMP-2, and MMP-9 expressions, eventually leading to enhanced proliferation and migration of ASM cells in vitro.
Keywords: Airway remodeling; Airway smooth muscle cells; KLF4; MMP-2; miRNA-145; p21.