TY - JOUR
T1 - Plant miRNA osa-miR172d-5p suppressed lung fibrosis by targeting Tab1
AU - Kumazoe, Motofumi
AU - Ogawa, Fumiyo
AU - Hikida, Ai
AU - Shimada, Yu
AU - Yoshitomi, Ren
AU - Watanabe, Ryoya
AU - Onda, Hiroaki
AU - Fujimura, Yoshinori
AU - Tachibana, Hirofumi
N1 - Funding Information:
This work was supported in part by JSPS KAKENHI Grant no. JP20H05683 for H. Tachibana and JSPS KAKENHI Grant no. JP20K05960 for M Kumazoe. We would like to thank the Research Support Center, Research Center for Human Disease Modelling, Kyushu University Graduate School of Medical Sciences, and Center for Advanced Instrumental and Educational Supports, Faculty of Agriculture, Kyushu University for the technical assistance.
Funding Information:
This work was supported in part by JSPS KAKENHI Grant no. JP20H05683 for H. Tachibana and JSPS KAKENHI Grant no. JP20K05960 for M Kumazoe. We would like to thank the Research Support Center, Research Center for Human Disease Modelling, Kyushu University Graduate School of Medical Sciences, and Center for Advanced Instrumental and Educational Supports, Faculty of Agriculture, Kyushu University for the technical assistance.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Lung fibrosis, including idiopathic pulmonary fibrosis, is an intractable disease accompanied by an irreversible dysfunction in the respiratory system. Its pathogenesis involves the transforming growth factorβ (TGFβ)-induced overproduction of the extracellular matrix from fibroblasts; however, limited countermeasures have been established. In this study, we identified osa-miR172d-5p, a plant-derived microRNA (miR), as a potent anti-fibrotic miR. In silico analysis followed by an in vitro assay based on human lung fibroblasts demonstrated that osa-miR172d-5p suppressed the gene expression of TGF-β activated kinase 1 (MAP3K7) binding protein 1 (Tab1). It also suppressed the TGFβ-induced fibrotic gene expression in human lung fibroblasts. To assess the anti-fibrotic effect of osa-miR172d-5p, we established bleomycin-induced lung fibrosis models to demonstrate that osa-miR172d-5p ameliorated lung fibrosis. Moreover, it suppressed Tab1 expression in the lung tissues of bleomycin-treated mice. In conclusion, osa-miR172d-5p could be a potent candidate for the treatment of lung fibrosis, including idiopathic pulmonary fibrosis.
AB - Lung fibrosis, including idiopathic pulmonary fibrosis, is an intractable disease accompanied by an irreversible dysfunction in the respiratory system. Its pathogenesis involves the transforming growth factorβ (TGFβ)-induced overproduction of the extracellular matrix from fibroblasts; however, limited countermeasures have been established. In this study, we identified osa-miR172d-5p, a plant-derived microRNA (miR), as a potent anti-fibrotic miR. In silico analysis followed by an in vitro assay based on human lung fibroblasts demonstrated that osa-miR172d-5p suppressed the gene expression of TGF-β activated kinase 1 (MAP3K7) binding protein 1 (Tab1). It also suppressed the TGFβ-induced fibrotic gene expression in human lung fibroblasts. To assess the anti-fibrotic effect of osa-miR172d-5p, we established bleomycin-induced lung fibrosis models to demonstrate that osa-miR172d-5p ameliorated lung fibrosis. Moreover, it suppressed Tab1 expression in the lung tissues of bleomycin-treated mice. In conclusion, osa-miR172d-5p could be a potent candidate for the treatment of lung fibrosis, including idiopathic pulmonary fibrosis.
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U2 - 10.1038/s41598-023-29188-6
DO - 10.1038/s41598-023-29188-6
M3 - Article
C2 - 36746980
AN - SCOPUS:85147460543
SN - 2045-2322
VL - 13
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 2128
ER -