Mukherjee Arnab, Vankamamidi Sai Eashan, Ks Mukunthan
Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Manipal, India.
Sci Rep. 2025 Jul 12;15(1):25251. doi: 10.1038/s41598-025-11473-1.
Cadmium chloride (CdCl₂), a highly toxic environmental pollutant, significantly impacts kidney health, particularly in the proximal tubular cells, where it induces oxidative stress and lipid peroxidation. The specific mechanisms underlying cadmium toxicity remain unclear. It is hypothesized that it is mediated by microRNAs (miRNAs). These non-coding RNAs regulate gene expression by promoting mRNA degradation and translational repression. In this study, microarray data from HK-2 cells exposed to CdCl₂ was analyzed, revealing increased oxidative stress and disrupted mitochondrial function. The prolonged cadmium exposure disrupted gene expression and induced persistent toxicity. Notably, six miRNAs predominantly modulated the hub genes. A molecular interaction study of miRNA-mRNA duplexes indicated a strong interaction with the argonaute (AGO) protein of the RNA-induced silencing complex (RISC), suggesting that miRNA-mediated gene silencing plays a crucial role in cadmium-induced renal damage. These findings highlight the critical role of miRNAs in modulating cadmium toxicity and suggest their potential as biomarkers for cadmium-induced renal dysfunction.
氯化镉（CdCl₂）是一种剧毒的环境污染物，对肾脏健康有显著影响，尤其是在近端肾小管细胞中，它会诱导氧化应激和脂质过氧化。镉毒性的具体机制尚不清楚。据推测，其由微小RNA（miRNA）介导。这些非编码RNA通过促进mRNA降解和翻译抑制来调节基因表达。在本研究中，分析了暴露于CdCl₂的HK-2细胞的微阵列数据，结果显示氧化应激增加且线粒体功能受到破坏。长时间的镉暴露扰乱了基因表达并诱导了持续性毒性。值得注意的是，六种miRNA主要调节枢纽基因。对miRNA-mRNA双链体的分子相互作用研究表明，其与RNA诱导沉默复合体（RISC）的AGO蛋白有强烈相互作用，这表明miRNA介导的基因沉默在镉诱导的肾损伤中起关键作用。这些发现突出了miRNA在调节镉毒性中的关键作用，并表明它们作为镉诱导肾功能障碍生物标志物的潜力。
