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Exosome‑encapsulated miR‑26a attenuates aldosterone‑induced tubulointerstitial fibrosis by inhibiting the CTGF/SMAD3 signaling pathway

  • Authors:
    • Hui Zheng
    • Jialing Ji
    • Tangming Zhao
    • E Wang
    • Aiqing Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, P.R. China, Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, P.R. China
    Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 11
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    Published online on: December 12, 2022
       https://doi.org/10.3892/ijmm.2022.5214
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Abstract

Renal tubulointerstitial fibrosis (TIF) is a hallmark in the continuous progression of chronic kidney disease (CKD), in which excessive activation of the renin‑angiotensin‑­aldosterone system serves a crucial role. Currently, there are no targeted therapies for the progression of TIF. microRNA (miR)‑26a may be an ideal anti‑fibrosis candidate molecule; however, the effect of miR‑26 on aldosterone (ALD)‑induced TIF remains unclear. This study aimed to elucidate the role of miR‑26a in ALD‑induced TIF. In the present study, we hypothesized that delivery of miR‑26a by exosomes could attenuate ALD‑induced TIF. miR‑26a expression was downregulated in the kidney of ALD‑induced mice compared with the mice in the sham group. Exosome‑encapsulated miR‑26a (Exo‑miR‑26a) was manufactured and injected into ALD‑treated mice through the tail vein. In vivo experiments showed that Exo‑miR‑26a alleviated the downregulated miR‑26a expression in the kidney, tubular injury and ALD‑induced TIF, which was determined using Masson's trichrome staining and assessment of lipocalin 2, α‑smooth muscle actin, collagen I and fibronectin expression. Moreover, in vitro experiments revealed that Exo‑miR‑26a inhibited epithelial‑mesenchymal transition and extracellular matrix deposition in mouse tubular epithelial cells. Mechanistically, overexpressing miR‑26a led to decreased expression levels of connective tissue growth factor by directly binding to its 3'‑UTR and inhibiting the activation of SMAD3. These findings demonstrated that the exosomal delivery of miR‑26a may alleviate ALD‑induced TIF, which may provide new insights into the treatment of CKD.
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Copy and paste a formatted citation
Spandidos Publications style
Zheng H, Ji J, Zhao T, Wang E and Zhang A: Exosome‑encapsulated miR‑26a attenuates aldosterone‑induced tubulointerstitial fibrosis by inhibiting the CTGF/SMAD3 signaling pathway. Int J Mol Med 51: 11, 2023.
APA
Zheng, H., Ji, J., Zhao, T., Wang, E., & Zhang, A. (2023). Exosome‑encapsulated miR‑26a attenuates aldosterone‑induced tubulointerstitial fibrosis by inhibiting the CTGF/SMAD3 signaling pathway. International Journal of Molecular Medicine, 51, 11. https://doi.org/10.3892/ijmm.2022.5214
MLA
Zheng, H., Ji, J., Zhao, T., Wang, E., Zhang, A."Exosome‑encapsulated miR‑26a attenuates aldosterone‑induced tubulointerstitial fibrosis by inhibiting the CTGF/SMAD3 signaling pathway". International Journal of Molecular Medicine 51.2 (2023): 11.
Chicago
Zheng, H., Ji, J., Zhao, T., Wang, E., Zhang, A."Exosome‑encapsulated miR‑26a attenuates aldosterone‑induced tubulointerstitial fibrosis by inhibiting the CTGF/SMAD3 signaling pathway". International Journal of Molecular Medicine 51, no. 2 (2023): 11. https://doi.org/10.3892/ijmm.2022.5214
Copy and paste a formatted citation
x
Spandidos Publications style
Zheng H, Ji J, Zhao T, Wang E and Zhang A: Exosome‑encapsulated miR‑26a attenuates aldosterone‑induced tubulointerstitial fibrosis by inhibiting the CTGF/SMAD3 signaling pathway. Int J Mol Med 51: 11, 2023.
APA
Zheng, H., Ji, J., Zhao, T., Wang, E., & Zhang, A. (2023). Exosome‑encapsulated miR‑26a attenuates aldosterone‑induced tubulointerstitial fibrosis by inhibiting the CTGF/SMAD3 signaling pathway. International Journal of Molecular Medicine, 51, 11. https://doi.org/10.3892/ijmm.2022.5214
MLA
Zheng, H., Ji, J., Zhao, T., Wang, E., Zhang, A."Exosome‑encapsulated miR‑26a attenuates aldosterone‑induced tubulointerstitial fibrosis by inhibiting the CTGF/SMAD3 signaling pathway". International Journal of Molecular Medicine 51.2 (2023): 11.
Chicago
Zheng, H., Ji, J., Zhao, T., Wang, E., Zhang, A."Exosome‑encapsulated miR‑26a attenuates aldosterone‑induced tubulointerstitial fibrosis by inhibiting the CTGF/SMAD3 signaling pathway". International Journal of Molecular Medicine 51, no. 2 (2023): 11. https://doi.org/10.3892/ijmm.2022.5214
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