Open Access

Metformin attenuates renal interstitial fibrosis through upregulation of Deptor in unilateral ureteral obstruction in rats

  • Authors:
    • Yanxia Wang
    • Yan Wang
    • Yong Li
    • Linghong Lu
    • Yingxian Peng
    • Shu Zhang
    • Anzhou Xia
  • View Affiliations

  • Published online on: August 26, 2020     https://doi.org/10.3892/etm.2020.9144
  • Article Number: 17
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Renal interstitial fibrosis (RIF) is a common pathological process that accompanies chronic kidney disease (CKD) and that progresses to end‑stage renal failure (ESRD). Accumulating evidence has revealed that persistent mammalian target of rapamycin (mTOR) activation in kidneys is closely associated with the occurrence and progression of CKD. The DEP domain‑containing mTOR interacting protein (Deptor) is an endogenous negative regulator of mTOR. Metformin can attenuate renal fibrosis in an animal model of diabetic nephropathy. Previous studies demonstrated that metformin can attenuate renal fibrosis in several models of CKD. However, the precise mechanisms of this effect are not well understood. The present study aimed to examine the mechanism of action of metformin on unilateral ureteral obstruction (UUO)‑induced RIF in rats in vivo. Sprague‑Dawley rats were randomly divided into a sham‑operated group, three UUO groups examined at different time points (3, 7 and 14 days after UUO surgery), and three metformin‑treated groups, treated with three different concentrations of metformin. The metformin‑treated groups were administered metformin orally every day for 14 consecutive days following surgery. The protein expression levels of Deptor, α‑smooth muscle actin (α‑SMA), phosphorylated (p‑)mTOR, p‑ribosomal protein S6 kinase (p‑p70S6K) and CD68 were assessed. The present results suggested that, following UUO, there was a significant reduction of Deptor expression, and an increase in collagen deposition in the extracellular matrix over time, accompanied by an increased expression of several proteins including CD68, α‑SMA, p‑mTOR and p‑p70S6K. Notably, metformin treatment reversed these effects. In conclusion, the present results suggested that metformin attenuated RIF of UUO rats, and the mechanism of action was found to be associated with the increase in Deptor expression and inhibition of the mTOR/p70S6K pathway in the kidneys of UUO rats.
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November-2020
Volume 20 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Wang Y, Wang Y, Li Y, Lu L, Peng Y, Zhang S and Xia A: Metformin attenuates renal interstitial fibrosis through upregulation of Deptor in unilateral ureteral obstruction in rats. Exp Ther Med 20: 17, 2020
APA
Wang, Y., Wang, Y., Li, Y., Lu, L., Peng, Y., Zhang, S., & Xia, A. (2020). Metformin attenuates renal interstitial fibrosis through upregulation of Deptor in unilateral ureteral obstruction in rats. Experimental and Therapeutic Medicine, 20, 17. https://doi.org/10.3892/etm.2020.9144
MLA
Wang, Y., Wang, Y., Li, Y., Lu, L., Peng, Y., Zhang, S., Xia, A."Metformin attenuates renal interstitial fibrosis through upregulation of Deptor in unilateral ureteral obstruction in rats". Experimental and Therapeutic Medicine 20.5 (2020): 17.
Chicago
Wang, Y., Wang, Y., Li, Y., Lu, L., Peng, Y., Zhang, S., Xia, A."Metformin attenuates renal interstitial fibrosis through upregulation of Deptor in unilateral ureteral obstruction in rats". Experimental and Therapeutic Medicine 20, no. 5 (2020): 17. https://doi.org/10.3892/etm.2020.9144