Diagnostic Value of miR-126-5p in Sepsis-Induced Acute Kidney Injury and its Molecular Mechanism via CASP3.

IF 2.7 3区医学 Q2 CRITICAL CARE MEDICINE

SHOCK Pub Date : 2026-10-01 Epub Date: 2026-07-03 DOI:10.1097/SHK.0000000000002905

Xiaowei Yuan, Wanyi Tan, Yuan Zhang, Lin He

{"title":"Diagnostic Value of miR-126-5p in Sepsis-Induced Acute Kidney Injury and its Molecular Mechanism via CASP3.","authors":"Xiaowei Yuan, Wanyi Tan, Yuan Zhang, Lin He","doi":"10.1097/SHK.0000000000002905","DOIUrl":null,"url":null,"abstract":"Background: As a common and devastating complication of sepsis, sepsis-induced acute kidney injury (SAKI) confers a significant risk of mortality.Purpose: This work focused on the utility of miR-126-5p as a biomarker for SAKI.Methods: A total of 95 patients with SAKI and 70 patients with sepsis alone were enrolled. Serum levels of miR-126-5p and Caspase-3 (CASP3) were measured using reverse transcription quantitative polymerase chain reaction. The regulatory interaction between miR-126-5p and CASP3 was validated using a dual-luciferase reporter assay. Cell proliferation, apoptosis, inflammatory cytokine levels, and oxidative stress markers were evaluated using the cell counting kit-8 assay, flow cytometry, enzyme-linked immunosorbent assay, and corresponding commercial kits, respectively.Results: Serum miR-126-5p levels were downregulated in SAKI patients and showed significant negative correlations with kidney injury markers, including serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Overexpression of miR-126-5p in lipopolysaccharide-stimulated HK-2 cells was shown in vitro to facilitate cell proliferation, restrain apoptosis, and suppress the production of interleukin-1β, interleukin-6, and tumor necrosis factor-α. Concurrently, it reduced oxidative stress markers, reactive oxygen species, and malondialdehyde, and enhanced superoxide dismutase activity. Mechanistically, CASP3 was identified as a direct downstream target of miR-126-5p, and its expression was negatively regulated by miR-126-5p. Furthermore, overexpression of CASP3 significantly reversed the protective effects of miR-126-5p in vitro .Conclusions: miR-126-5p showed diagnostic value for SAKI and exerted a protective effect in vitro through targeted regulation of CASP3 expression.","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"950-959"},"PeriodicalIF":2.7000,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"SHOCK","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/SHK.0000000000002905","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/7/3 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}

引用次数: 0

Abstract

Background: As a common and devastating complication of sepsis, sepsis-induced acute kidney injury (SAKI) confers a significant risk of mortality.

Purpose: This work focused on the utility of miR-126-5p as a biomarker for SAKI.

Methods: A total of 95 patients with SAKI and 70 patients with sepsis alone were enrolled. Serum levels of miR-126-5p and Caspase-3 (CASP3) were measured using reverse transcription quantitative polymerase chain reaction. The regulatory interaction between miR-126-5p and CASP3 was validated using a dual-luciferase reporter assay. Cell proliferation, apoptosis, inflammatory cytokine levels, and oxidative stress markers were evaluated using the cell counting kit-8 assay, flow cytometry, enzyme-linked immunosorbent assay, and corresponding commercial kits, respectively.

Results: Serum miR-126-5p levels were downregulated in SAKI patients and showed significant negative correlations with kidney injury markers, including serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Overexpression of miR-126-5p in lipopolysaccharide-stimulated HK-2 cells was shown in vitro to facilitate cell proliferation, restrain apoptosis, and suppress the production of interleukin-1β, interleukin-6, and tumor necrosis factor-α. Concurrently, it reduced oxidative stress markers, reactive oxygen species, and malondialdehyde, and enhanced superoxide dismutase activity. Mechanistically, CASP3 was identified as a direct downstream target of miR-126-5p, and its expression was negatively regulated by miR-126-5p. Furthermore, overexpression of CASP3 significantly reversed the protective effects of miR-126-5p in vitro .

Conclusions: miR-126-5p showed diagnostic value for SAKI and exerted a protective effect in vitro through targeted regulation of CASP3 expression.

查看原文本刊更多论文

miR-126-5p在脓毒症急性肾损伤中的诊断价值及其通过CASP3表达的分子机制

背景：脓毒症引起的急性肾损伤（SAKI）是一种常见且具有破坏性的并发症，具有很高的死亡率。目的：本工作的重点是miR-126-5p作为SAKI的生物标志物的效用。方法：共纳入95例SAKI患者和70例单纯脓毒症患者。采用RT-qPCR检测血清miR-126-5p和CASP3水平。miR-126-5p和CASP3之间的调节相互作用通过双荧光素酶报告试验得到验证。分别使用CCK-8法、流式细胞术、ELISA和相应的商用试剂盒评估细胞增殖、凋亡、炎症细胞因子水平和氧化应激标志物。结果：血清miR-126-5p水平在SAKI患者中下调，并与肾损伤标志物呈显著负相关，包括血清肌酐（Scr）、胱抑素C （Cys-C）、中性粒细胞明胶酶相关脂钙蛋白（NGAL）和肾损伤分子-1 （KIM-1）。体外实验显示，在脂多糖（LPS）刺激的HK-2细胞中，miR-126-5p过表达可促进细胞增殖，抑制细胞凋亡，抑制白细胞介素-1β (IL-1β)、白细胞介素-6 （IL-6）和肿瘤坏死因子-α (TNF-α)的产生。同时，降低氧化应激标志物、活性氧（ROS）和丙二醛（MDA），增强超氧化物歧化酶（SOD）活性。机制上，CASP3被确定为miR-126-5p的直接下游靶点，其表达受到miR-126-5p的负调控。此外，CASP3的过表达在体外显著逆转了miR-126-5p的保护作用。结论：MiR-126-5p对SAKI具有诊断价值，并通过靶向调控CASP3表达在体外发挥保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

SHOCK 医学-外科

CiteScore

6.20

自引率

3.20%

发文量

199

审稿时长

1 months

期刊介绍： SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.