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The lncRNA H19 Mediates Pulmonary Fibrosis by Regulating the miR-196a/COL1A1 Axis

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Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by lung fibroblasts accumulation and extracellular matrix (ECM) deposition. Recently, long-noncoding RNAs (lncRNAs) have emerged as critical regulators and prognostic markers in several diseases including IPF. In the present study, we found that the expression of H19 was significantly increased in transforming growth factor-β (TGF-β)-induced fibroblast proliferation and bleomycin-(BLM) induced lung fibrosis (p < 0.05). We further demonstrated that H19 was a direct target of miR-196a and was associated with COL1A1 expression by sponging miR-196a. Moreover, downregulation of H19 alleviated fibroblast activation and lung fibrosis, and this effect was blocked by a miR-196a inhibitor. In conclusion, our results suggest that lncRNA H19 has a promotive effect on BLM-induced IPF, and it functions as a molecular sponge of miR-196a, which provides a novel therapeutic target for IPF.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China [grant numbers 81673014, 81372347, and 81370174], Outstanding Academic Leaders Plan of Shanghai Municipal Science and Technology Committee [grant number 16XD1403100], and National Key R&D Plan [grant number 2017YFA0104600].

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    Authors and Affiliations

    1. Department of Respiratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China

      Qingchun Lu, Zhongliang Guo, Wang Xie & Dongyi Zhu

    2. Department of Intensive Care Unit, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China

      Wenjing Jin

    3. Department of Emergency and Critical Care Medicine, Shanghai Pudong New Area People’s Hospital, Shanghai, 201299, China

      Song Chen

    4. Department of Respiratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

      Tao Ren

    Author notes

    1. Qingchun Lu and Zhongliang Guo contributed equally to this work.

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      1. Qingchun Lu
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      Correspondence to Tao Ren.

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      Lu, Q., Guo, Z., Xie, W. et al. The lncRNA H19 Mediates Pulmonary Fibrosis by Regulating the miR-196a/COL1A1 Axis. Inflammation 41, 896–903 (2018). https://doi.org/10.1007/s10753-018-0744-4

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