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Regulation of type I collagen expression by microRNA-29 following ionizing radiation

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Abstract

Radiation-induced fibrosis (RIF) is thought to involve the excessive accumulation of collagen and other extracellular matrix components; previously, we reported that ionizing radiation increased the type I collagen expression and that transforming growth factor (TGF)-β was involved in this increase through activating its downstream mediator, Smad3. A recent study found that microRNAs (miRNAs)—small, noncoding sequences approximately 20 nucleotides long—negatively regulate the gene expression posttranscriptionally, and it has been suggested that miRNAs play essential roles in cellular processes, including fibrosis. However, their role in the development of RIF remains unexplored. In the present study, we examined the effects of miRNA on the expression of type I collagen induced by ionizing radiation and the mechanisms underlying the miRNA expression observed following ionizing radiation. We analyzed the regulation of miRNA following ionizing radiation by an miRNA real-time PCR, and found that miR-29 family members were downregulated in irradiated mouse fibroblasts and directly targeted type I collagen genes by specifically binding to the 3ʹ untranslated region. We also found that the overexpression of miR-29 inhibited the ionizing radiation-induced expression of type I collagen, whereas the knockdown of miR-29 enhanced it. In addition, TGF-β/Smad-signaling significantly decreased the transcription of miR-29, whereas the inhibition of this signaling pathway cancelled this decrease. In conclusion, miR-29 was involved in the regulation of type I collagen expression through the TGF-β/Smad-signaling pathway in irradiated cells, suggesting that miR-29 may be an important regulator of RIF.

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Abbreviations

RIF:

Radiation-induced fibrosis

miRNA:

MicroRNA

CHIP assay:

Chromatin immunoprecipitation assay

ECM:

Extracellular matrix

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Acknowledgements

We thank Mr. K. Kai, Ms. H. Sato, and the staff members of the Department of Matrix Medicine, Faculty of Medicine, Oita University. 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, Yufu, Japan

    Ryoji Hamanaka & Miki Nakamura-Ota

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

    Ryoji Hamanaka

  4. Department of Matrix Medicine, Faculty of Medicine, Oita University, Yufu, Japan

    Juan Juan Zhang, 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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  4. Juan Juan Zhang
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Correspondence to Hiroyuki Yano.

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Yano, H., Hamanaka, R., Nakamura-Ota, M. et al. Regulation of type I collagen expression by microRNA-29 following ionizing radiation. Radiat Environ Biophys 57, 41–54 (2018). https://doi.org/10.1007/s00411-017-0723-4

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  • DOI: https://doi.org/10.1007/s00411-017-0723-4

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