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Swimming exercise activates peroxisome proliferator-activated receptor-alpha and mitigates age-related renal fibrosis in rats

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Abstract

Aging results in progressive decline of renal function as well as histological alterations including glomerulosclerosis and interstitial fibrosis. The objective of current study was to test the benefits of moderate swimming exercise in aged rats on renal function and structure and investigate its molecular mechanisms. Aged rats of 21-months old were given moderate swimming exercise for 12 weeks. Swimming exercise in aged rats led to reduced plasma levels of creatinine and blood urea nitrogen. Periodic acid-Schiff staining results revealed reduced renal injury scores in aged rats after swimming exercise. Swimming exercise in aged rats mitigated renal fibrosis and downregulated the mRNA expression of Acta2, Fn, Col1a, Col4a, and Tgfb1 in kidneys. Swimming exercise in aged rats attenuated lipid accumulation and reduced levels of triglyceride in kidneys. Swimming exercise in aged rats abated oxidative stress, evidenced by reduced MDA levels and increased MnSOD activities in kidneys. Swimming exercise in aged rats inhibited NF-κB activities and reduced renal expression of pro-inflammatory cytokines including MCP-1, IL-1β and IL-6. Mechanistically, swimming exercise restored mRNA and protein expression of PPAR-α in kidney of aged rats. Furthermore, swimming exercise in aged rats increased expression of PPAR-α-targeting microRNAs including miR-21 and miR-34a. Collectively, swimming exercise activated PPAR-α, which partly explained the benefits of moderate swimming exercise in aging kidneys.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BUN :

Blood urea nitrogen

MCP-1 :

Macrophage chemoattractant protein 1

MDA :

Malondialdehyde

PAS :

Periodic acid-Schiff

PPAR- α :

Peroxisome proliferator-activated receptor alpha

qRT-PCR :

Quantitative real-time PCR

ROS :

Reactive oxygen species

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81971017 to Yongsheng Yu).

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Conception and design of the experiments: HXZ, ZZ, HDZ. Collection, analysis and interpretation of data: HXZ, ZZ, FH, QFW, YSY, HDZ. Drafting the article: HDZ.

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Correspondence to Hao-Dong Zhao.

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Zhao, HX., Zhang, Z., Hu, F. et al. Swimming exercise activates peroxisome proliferator-activated receptor-alpha and mitigates age-related renal fibrosis in rats. Mol Cell Biochem 478, 1109–1116 (2023). https://doi.org/10.1007/s11010-022-04581-3

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  • DOI: https://doi.org/10.1007/s11010-022-04581-3

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