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| Effect of hesperidin on high glucose induced autophagy in glomerular mesangial cells by regulating the mTOR/HIF-1α pathway |
| Hits 495 Download times 232 Received:August 15, 2024 |
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| DOI
10.11656/j.issn.1672-1519.2025.01.15 |
| Key Words
hesperidin;mTOR/HIF-1α pathway;high glucose;glomerular mesangial cell;autophagy |
| Author Name | Affiliation | E-mail | | LI Miao | Department of Nephrology, Zhengzhou Yihe Hospital, Zhengzhou 450018, China | | | LI Rui | Department of Nephrology, Zhengzhou Yihe Hospital, Zhengzhou 450018, China | | | YANG Xiaofang | Department of Nephrology, Zhengzhou Yihe Hospital, Zhengzhou 450018, China | | | FENG Wenjun | Department of Nephrology, Zhengzhou Yihe Hospital, Zhengzhou 450018, China | Fw1990699@163.com |
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| Abstract
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| [Objective] To investigate the effect of hesperidin on autophagy in glomerular mesangial cells induced by high glucose by regulating the mammalian target of rapamycin（mTOR）/hypoxia-inducible factor-1α（HIF-1α） pathway. [Methods] SV40 MES-13 cells with good growth were randomly separated into control group（without treatment），mannitol group（30 mmol/L mannitol treatment），high glucose group（30 mmol/L glucose），different doses hesperidin groups（30 mmol/L，60 mmol/L hesperidin treatment），and 60 mmol/L hesperidin+insulin-like growth factor-1（IGF-1） group（60 mmol/L hesperidin，100 ng/mL IGF-1 treatment）. Methylthiazolyldiphenyl-tetrazolium bromide（MTT） and 5-ethynyl-2’-deoxyuridine（EdU） were used to detect cell proliferation. Enzyme linked immunosorbent assay（ELISA） was applied to detect levels of tumor necrosis factor-α（TNF-α） and interleukin（IL）-1β. Flow cytometry was applied to detect the level of cell apoptosis. Real-time quantitative PCR（qRT-PCR） was applied to detect the mRNA expression levels of microtubule-associated protein 1 light chain 3（LC3），p62，and autophagy related gene 5（ATG5）. Western blot was applied to detect the expression levels of p-PI3K，p-Akt，p-mTOR，PI3K，Akt，mTOR，and HIF-1α related proteins. [Results] Compared with the control group，there was no statistically obvious difference in absorbance value，EdU positivity rate，TNF-α，IL-1β levels，apoptosis rate，LC3，p62，ATG5 mRNA expression，p-PI3K/PI3K，p-Akt/Akt，p-mTOR/mTOR，and HIF-1α expression in the mannitol group（P>0.05）. After high glucose induction，the absorbance value，EdU positivity rate，TNF-α，IL-1β levels，p62 mRNA expression，p-PI3K/PI3K，p-Akt/Akt，p-mTOR/mTOR，HIF-1α expression were obviously increased compared to the control group and mannitol group，while apoptosis rate，LC3，and ATG5 mRNA expression were obviously decreased（P<0.05）. After treatment with different doses of hesperidin，the absorbance value，EdU positive rate，TNF-α，IL-1β levels，p62 mRNA expression，p-PI3K/PI3K，p-Akt/Akt，p-mTOR/mTOR，and HIF-1α expression were obviously reduced compared to the high glucose group. The apoptosis rate，LC3，and ATG5 mRNA expression were obviously increased，and there was a difference between groups（P<0.05）. After treatment with 60 mmol/L hesperidin combined with IGF-1，the absorbance value，EdU positive rate，TNF-α，IL-1β levels，p62 mRNA expression，p-PI3K/PI3K，p-Akt/Akt，p-mTOR/mTOR，and HIF-1α expression were obviously increased compared to 60 mmol/L hesperidin alone treatment. The apoptosis rate，LC3，and ATG5 mRNA expression were obviously reduced（P<0.05）. [Conclusion] Hesperidin promotes high glucose induced autophagy in mesangial cells and inhibits their proliferation by regulating the mTOR/HIF-1α pathway. |
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