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肾脏衰老相关疾病中Klotho与SIRT1表达之间的关系

The Relationship Between Klotho and SIRT1 Expression in Renal Aging Related Disease.

作者信息

Su Hong, Gao Diansa, Chen Yanlin, Zuo Zhong

机构信息

The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.

The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, Chongqing, 400016, People's Republic of China.

出版信息

Int J Gen Med. 2022 Oct 21;15:7885-7893. doi: 10.2147/IJGM.S384119. eCollection 2022.

Abstract

BACKGROUND

This study focused on renal arteriosclerosis and aimed to explore the relationship between Klotho and SIRT1 by morphological staining, which will help to provide new ideas for the treatment of renal-aging-related diseases and a theoretical basis for the development of new drugs.

METHODS

Kidney tissue samples were collected from patients who underwent nephrectomy. HK-2 cells were cultured. The Hematoxylin-eosin (HE) staining, Periodic Acid-Schiff (PAS) staining, Masson's Trichrome staining, Immunohistochemistry (IHC) staining, Immunofluorescence (ICC) and bioinformatics means were used for this study.

RESULTS

HE staining showed that glomerulosclerosis was atrophic and cast was significantly increased luminal narrowing of renal arterioles in aging group. PAS staining showed that the number of podocytes was reduced, the mesangial matrix expansion and the intimal fibrosis of renal arterioles. Masson's trichrome staining showed that there was massive collagen proliferation in the tubulointerstitial in aging group, as well as intimal thickening and fibrin deposition in the tubular walls of arterioles. IHC staining showed that the expression of Klotho and SIRT1 protein was downregulated in aging group and the trend of the two was positively correlated (P < 0.01). Klotho and SIRT1 co-localized in HK-2 cells and kidney tissue. The GEPIA database analysis showed a significant positive correlation between Klotho and SIRT1 in multiple human tissues and tumors.

CONCLUSION

Glomerulosclerosis in aging group is accompanied by low expression of Klotho and SIRT1 in renal tissue, and Klotho is positively correlated with SIRT1. Klotho-SIRT1 pathway may be involved in the occurrence and development of renal-aging-related diseases.

摘要

背景

本研究聚焦于肾动脉硬化,旨在通过形态学染色探索Klotho与SIRT1之间的关系,这将有助于为肾衰老相关疾病的治疗提供新思路,并为新药研发提供理论依据。

方法

收集接受肾切除术患者的肾组织样本。培养HK-2细胞。本研究采用苏木精-伊红(HE)染色、过碘酸-希夫(PAS)染色、Masson三色染色、免疫组织化学(IHC)染色、免疫荧光(ICC)及生物信息学方法。

结果

HE染色显示,衰老组肾小球硬化萎缩,肾小动脉管腔明显狭窄,管型显著增多。PAS染色显示,足细胞数量减少,系膜基质扩张,肾小动脉内膜纤维化。Masson三色染色显示,衰老组肾小管间质有大量胶原增生,小动脉管壁内膜增厚及纤维蛋白沉积。IHC染色显示,衰老组Klotho和SIRT1蛋白表达下调,二者呈正相关趋势(P<0.01)。Klotho和SIRT1在HK-2细胞和肾组织中共同定位。GEPIA数据库分析显示,在多种人体组织和肿瘤中,Klotho与SIRT1呈显著正相关。

结论

衰老组肾小球硬化伴肾组织中Klotho和SIRT1低表达,且Klotho与SIRT1呈正相关。Klotho-SIRT1通路可能参与肾衰老相关疾病的发生发展。

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