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Mir-204-5p alleviates mitochondrial dysfunction by targeting IGFBP5 in diabetic cataract

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Abstract

Background

Cataract contributes to visual impairment worldwide, and diabetes mellitus accelerates the formation and progression of cataract. Here we found that the expression level of miR-204-5p was diminished in the lens epithelium with anterior lens capsule of cataract patients compared to normal donors, and decreased more obviously in those of diabetic cataract (DC) patients. However, the contribution and mechanism of miR-204-5p during DC development remain elusive.

Methods and result

The mitochondrial membrane potential (MMP) was reduced in the lens epithelium with anterior lens capsule of DC patients and the H2O2-induced human lens epithelial cell (HLEC) cataract model, suggesting impaired mitochondrial functional capacity. Consistently, miR-204-5p knockdown by the specific inhibitor also attenuated the MMP in HLECs. Using bioinformatics and a luciferase assay, further by immunofluorescence staining and Western blot, we identified IGFBP5, an insulin-like growth factor binding protein, as a direct target of miR-204-5p in HLECs. IGFBP5 expression was upregulated in the lens epithelium with anterior lens capsule of DC patients and in the HLEC cataract model, and IGFBP5 knockdown could reverse the mitochondrial dysfunction in the HLEC cataract model.

Conclusions

Our results demonstrate that miR-204-5p maintains mitochondrial functional integrity through repressing IGFBP5, and reveal IGFBP5 may be a new therapeutic target and prognostic factor for DC.

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Funding

Supported by Qilu Health Outstanding Young Talents Program (A0241), the National Natural Science Foundation of China (82000851, 81970782), and the Natural Science Foundation of Shandong Province (ZR2020QH144).

Author information

Authors and Affiliations

  1. State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, China

    ** **e, Rui Cao, **aolei Wang & Yunhai Dai

  2. Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China

    ** **e, Rui Cao & Yunhai Dai

  3. Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, China

    Peng Chen

  4. Institute of Stem Cell Regeneration Medicine, School of Basic Medicine, Qingdao University, Qingdao, China

    Peng Chen

  5. Shandong First Medical University, **an, China

    Shilan Mao

  6. School of Ophthalmology, Shandong First Medical University, Qingdao, China

    Shilan Mao

  7. Weifang Medical University, Weifang, China

    **nyi Zang

  8. The Affiliated Hospital of Qingdao University, Qingdao, China

    Wenhui Liu

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  1. ** **e
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  2. Peng Chen
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Contributions

J. X., P. C. conducted experiments, S. M. collected human anterior lens capsule samples, X. Z., W.L. and R. C. analyzed most of the data and prepared the figures, J. X. and X. W. wrote and modified the manuscript, Y. D. and X. W. supervised the research.

Corresponding authors

Correspondence to **aolei Wang or Yunhai Dai.

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Ethical declaration

This study was approved by the Ethical Committee of Qingdao Eye Hospital affiliated with Shandong First Medical University (No:5-2021-008), and conducted in accordance with the provisions of the Declaration of Helsinki. The human materials were obtained with the consent of the participants and all participants signed consent prior to participation.

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**e, J., Chen, P., Mao, S. et al. Mir-204-5p alleviates mitochondrial dysfunction by targeting IGFBP5 in diabetic cataract. Mol Biol Rep 51, 755 (2024). https://doi.org/10.1007/s11033-024-09701-4

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