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

• Published in: Molecular biology reports 2024-12, Vol.51 (1), p.755
• Main Authors: Xie, Jin, Chen, Peng, Mao, Shilan, Zang, Xinyi, Cao, Rui, Liu, Wenhui, Wang, Xiaolei, Dai, Yunhai
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Bioinformatics; Biomedical and Life Sciences; Cataract - genetics; Cataract - metabolism; Cataract - pathology; Cataracts; Diabetes; Diabetes Complications - genetics; Diabetes Complications - metabolism; Diabetes mellitus; Epithelial cells; Epithelial Cells - metabolism; Epithelium; Female; Histology; Humans; Hydrogen peroxide; Immunofluorescence; Insulin-Like Growth Factor Binding Protein 5 - genetics; Insulin-Like Growth Factor Binding Protein 5 - metabolism; Insulin-like growth factor-binding protein 5; Lens, Crystalline - metabolism; Lens, Crystalline - pathology; Life Sciences; Male; Membrane potential; Membrane Potential, Mitochondrial; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Mitochondria; Mitochondria - metabolism; Morphology; Original Article; Therapeutic targets
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-024-09701-4

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.