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Advanced glycation end products promote the progression of chronic kidney diseases by targeting calpain 6

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Abstract

Advanced glycation end products (AGEs) are produced by glycosylation or oxidation of proteins and lipids and are tightly involved in the chronic kidney disease (CKD) process. Calpain 6 (CAPN6) is a non-classical calpain that has been reported to be overexpressed in CKD. This study aimed to explore the effects of AGEs in CKD progress and their correlation with CAPN6. AGEs production was measured using ELISA. The CCK-8 assay was used to test cell proliferation. mRNA and protein levels were tested using qRT-PCR and western blot. The progress of glycolysis was tested by calculating the ATP and ECAR content in HK-2 cells. The expression of AGEs and CAPN6 was significantly increased in patients with CKD3, CKD4, and CKD5. AGEs treatment inhibited cell proliferation and glycolysis and accelerated apoptosis. Additionally, CAPN6 knockdown effectively reversed the effects of AGEs in HK-2 cells. In addition, overexpressed CAPN6 played similar role to AGEs, which suppressed cell proliferation and glycolysis and facilitated apoptosis. Moreover, the administration of 2-DG, a glycolysis inhibitor, counteracted the effects of CAPN6 silencing in HK-2 cells. Mechanistically, CAPN6 interacts with NF-κB and PDTC reduced CAPN6 expression in HK-2 cells. This investigation revealed that AGEs facilitate CKD development in vitro by modulating the expression of CAPN6.

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Data availability

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

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Funding

This research was supported by the Topic of Shanghai Health Commission (No. 202040026), The third batch of key disciplines of Traditional Chinese medicine in Jiading District, Shanghai (No. 2020-JDZYYZDXM-01), Jiangqiao town community Health service Center famous old Chinese medicine (school) studio (No. 2021MLZYLPLPGZS-09), and Shanghai Jiading District Health system "Jiading Medical Star" young talent training program scientific research project (2019JDJYXX008).

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Author notes

  1. Yufan Zhang and Haiqiong Han: co-first authors.

Authors and Affiliations

  1. Department of TCM, Shanghai YangPu District KongJiang Hospital, ShuangYang Rd No. 480, YangPu District, Shanghai, 200093, China

    Yufan Zhang

  2. Shanghai Jiading District Jiangqiao Town Community Health Service Center, Rehabilitation Medicine Department, Jinyao Rd No. 100, Jiangqiao Town, Jiading District, Shanghai, China

    Haiqiong Han

  3. Department of Urology, Shanghai YangPu District KongJiang Hospital, ShuangYang Rd No. 480, YangPu District, Shanghai, 200093, China

    Yu Qian

  4. Department of Out-Patient Emergency, Shanghai YangPu District KongJiang Hospital, ShuangYang Rd No. 480, YangPu District, Shanghai, 200093, China

    Qiong Wang

  5. Geriatric Department, Shanghai YangPu District KongJiang Hospital, ShuangYang Rd No. 480, YangPu District, Shanghai, 200093, China

    Minmin Jiang

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  1. Yufan Zhang
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Contributions

MJ designed this project, participated in all experiments and revised the manuscript; YZ and HH performed the experiments and wrote the draft; YQ and QW participated in sample collection, analyzed the data, and edited the diagrams. All the authors contributed to the article and approved the submission of the definitive version.

Corresponding author

Correspondence to Minmin Jiang.

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The authors report there are no competing interests to declare.

Ethics approval and consent to participate

This study was approved by the independent ethics committee of Shanghai YangPu district KongJiang Hospital and strictly obeyed the Declaration of Helsinki.

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Handling editor: Y. Su.

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726_2023_3282_MOESM1_ESM.jpg

Supplementary file1Figure S1: Knockdown and overexpression of CAPN6 in human HK-2 cells. (A) and (B). qRT-PCR assay and western blot analysis were employed to confirm the transfection efficiency of shCAPN6 vector. (C) and (D). qRT-PCR assay and western blot analysis were employed to confirm the transfection efficiency of CAPN6 overexpression vector (JPG 87 KB)

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Zhang, Y., Han, H., Qian, Y. et al. Advanced glycation end products promote the progression of chronic kidney diseases by targeting calpain 6. Amino Acids 55, 903–912 (2023). https://doi.org/10.1007/s00726-023-03282-5

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  • DOI: https://doi.org/10.1007/s00726-023-03282-5

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