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MicroRNA-26 regulates the expression of CTGF after exposure to ionizing radiation

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Abstract

Radiation-induced fibrosis (RIF) is a serious complication that occurs after irradiation and which is caused by the deposition of extracellular matrix (ECM) proteins such as collagen. However, the underlying mechanisms, including the expression of the cytokines, that promote the RIF process, are not yet fully understood. MicroRNAs (miRNAs) have recently been suggested to act as post-transcriptional repressors for many genes; however, their role in the process of RIF remains to be elucidated. Our previous study showed that ionizing radiation increased the type I collagen expression through the activation of transforming growth factor (TGF)-β, while miR-29 repressed this increase. This study aimed to investigate the mechanisms by which the expression of connective tissue growth factor (CTGF), a downstream mediator of TGF-β, is controlled by miRNAs post-transcriptionally after exposure to ionizing radiation. The expression of CTGF in NIH-3T3 cells and mouse embryonic fibroblasts was increased by ionizing radiation. However, this increase was suppressed with a specific inhibitor of TGF-β receptor. Among the predictable miRNAs that target the CTGF gene, the expression of miR-26a was downregulated after exposure to ionizing radiation and this regulation was negatively mediated by TGF-β signaling. miR-26a negatively regulated the CTGF expression at the post-transcriptional level; however, ionizing radiation suppressed this negative regulation. In addition, the overexpression of miR-26a inhibited the expression of CTGF and type I collagen after irradiation. In conclusion, miR-26a modulates the expression of CTGF via TGF-β signaling in irradiated fibroblasts. The results suggest the potential application of miR-26a in the treatment of RIF.

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Abbreviations

RIF:

Radiation-induced fibrosis

miRNA:

MicroRNA

CTGF:

Connect tissue growth factor

ECM:

Extracellular matrix

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Acknowledgements

This work was supported by Grant-in-Aid for Young Scientists (No.15K19697 to H.Y.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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Authors and Affiliations

  1. Research Promotion Institute, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita, 879-5593, Japan

    Hiroyuki Yano

  2. Department of Cell Biology, Faculty of Medicine, Oita University, Oita, Japan

    Ryoji Hamanaka

  3. Department of Human Sciences, Oita University of Nursing and Human Sciences, Oita, Japan

    Ryoji Hamanaka

  4. Department of Matrix Biology and Medicine, Faculty of Medicine, Oita University, Oita, Japan

    Juan Juan Zhang, Mami Yano, Mariko Hida, Noritaka Matsuo & Hidekatsu Yoshioka

  5. Department of Clinical Examination, Shinbeppu Hospital, Beppu, Japan

    Hidekatsu Yoshioka

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  1. Hiroyuki Yano
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  2. Ryoji Hamanaka
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Correspondence to Hiroyuki Yano.

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Yano, H., Hamanaka, R., Zhang, J.J. et al. MicroRNA-26 regulates the expression of CTGF after exposure to ionizing radiation. Radiat Environ Biophys 60, 411–419 (2021). https://doi.org/10.1007/s00411-021-00915-9

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  • DOI: https://doi.org/10.1007/s00411-021-00915-9

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