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Effects of miRNA-145 on airway smooth muscle cells function

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Abstract

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.

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Acknowledgments

This work was supported by Grants from the National Natural Science Foundation of China (No. 81102252).

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Authors and Affiliations

  1. Department of Respiratory Medicine, The Second Affiliated Hospital of Xi’an Jiaotong University Medical College, 157 Xiwu Road, Xi’an Shaanxi, 710004, China

    Yun Liu, Xiuzhen Sun, Yuanyuan Wu, Ping Fang, Hongyang Shi, Jing Xu & Manxiang Li

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  1. Yun Liu
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  2. Xiuzhen Sun
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  3. Yuanyuan Wu
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Correspondence to Yun Liu.

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Liu, Y., Sun, X., Wu, Y. et al. Effects of miRNA-145 on airway smooth muscle cells function. Mol Cell Biochem 409, 135–143 (2015). https://doi.org/10.1007/s11010-015-2519-7

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