PUM2 Lowers HDAC9 mRNA Stability to Improve Contrast-Induced Acute Kidney Injury by Attenuating Oxidative Stress and Promoting Autophagy

作者：Wei Chen, Hengcheng Lu, Wenni Dai, Hao Li, Yinyin Chen, Guoyong Liu, Liyu He · 发表于：Diabetes & Metabolism Journal · 年份：2025 · DOI：10.4093/dmj.2024.0396 · 被引用次数：3 · 研究领域：Acute Kidney Injury Research、Histone Deacetylase Inhibitors Research、Hydrogen's biological and therapeutic effects

BACKGRUOUND: Contrast-induced acute kidney injury (CIAKI) is the third leading cause of hospital-acquired acute kidney injury and diabetes mellitus (DM) has been identified as a risk factor for CIAKI. However, the molecular mechanism underlying DM-CIAKI remains unclear and requires further investigation. METHODS: Mouse and cell models of DM-CIAKI were established. Kidney function was evaluated by measuring biochemical indicators and using hematoxylin and eosin staining. Gene and protein abundance was assessed using real-time quantitative reverse transcription polymerase chain reaction, immunohistochemistry, immunofluorescence, and Western blotting. Glutathione peroxidase, superoxide dismutase, and malondialdehyde were measured using commercial kits, and reactive oxygen species were detected using a dihydroethidium (DHE) probe and the 2',7'-dichlorofluorescein diacetate (DCFH-DA) method. Apoptosis in tissues and cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Cell viability and proliferation were measured using Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays. The interaction between pumilio RNA binding family member 2 (PUM2) and histone deacetylase 9 (HDAC9) was validated using RNA immunoprecipitation (RIP) and RNA pull-down assays. RESULTS: PUM2 expression was markedly reduced in DM-CIAKI models, whereas HDAC9 expression was notably increased. Subsequently, PUM2 silencing aggravated kidney injury in DM-CIAKI mice by ...