FBXW7 mediates high glucose‑induced SREBP‑1 expression in renal tubular cells of diabetic nephropathy under PI3K/Akt pathway regulation

Li,Lisha; Yang,Juxiang; Li,Fan; Gao,Fan; Zhu,Lin; Hao,Jun

doi:10.3892/mmr.2021.11872

FBXW7 mediates high glucose‑induced SREBP‑1 expression in renal tubular cells of diabetic nephropathy under PI3K/Akt pathway regulation

Authors:
- Lisha Li
- Juxiang Yang
- Fan Li
- Fan Gao
- Lin Zhu
- Jun Hao
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Affiliations: Department of Pathology, Cangzhou Hospital of Integrated TCM‑WM, Cangzhou, Hebei 061001, P.R. China, The Office of Basic Medical College, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Electromyogram, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050001, P.R. China
Published online on: January 26, 2021 https://doi.org/10.3892/mmr.2021.11872
Article Number: 233
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and lipid metabolism abnormality serves a key role in the pathogenesis of DN. Sterol regulatory element‑binding protein 1 (SREBP‑1) overexpression mediates aberrant lipid accumulation in renal tubular cells of DN. However, the exact mechanism involved in increased SREBP‑1 has not been fully elucidated. The aim of the present study was to explore the mechanism involved in SREBP‑1 upregulation. Diabetic mice and high glucose‑cultured HKC cells were chosen to detect the expression of FBXW7 and SREBP‑1 using immunohistochemistry, western blotting and PCR. The present study demonstrated that F‑box and WD repeat domain containing 7 (FBXW7) expression was decreased in renal tubular cells of diabetic mice. Moreover, the co‑expression of FBXW7 and SREBP‑1 was observed in renal tubular cells, but not in the glomeruli. High glucose‑induced the downregulation of FBXW7 expression in in vitro cultured HKC cells, which was accompanied by SREBP‑1 upregulation. In addition, overexpression of FBXW7 in HKC cells led to SREBP‑1 downregulation. By contrast, knockdown of FBXW7 caused SREBP‑1 upregulation in HKC cells. It was found that the PI3K/Akt signaling pathway was activated in high glucose‑stimulated HKC cells, and inhibition of PI3K/Akt pathway using LY294002 increased FBXW7 expression and decreased SREBP‑1 expression. Taken together, the present results suggested that FBXW7 mediated high glucose‑induced SREBP‑1 expression in renal tubular cells of DN, under the regulation of the PI3K/Akt signaling pathway.

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