miR-6722-3p improves sepsis-induced acute kidney injury by targeting CHI3L1

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-05-31 DOI:10.1016/j.tice.2025.103002

Lihua Zhang , Wan Pan , Jing Sun , Yinhong Song , Xuewei Gong

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引用次数: 0

Abstract

Objective

Acute kidney injury (AKI) is a common complication of sepsis, associated with increased morbidity and mortality. Recent studies suggested microRNAs (miRNAs) play a crucial role in the pathogenesis of AKI. However, the specific role and underlying mechanisms of miR-6722-3p in AKI remain poorly understood.

Methods

Male Sprague Dawley rats were subjected to cecum ligation and perforation (CLP) to establish a sepsis-induced AKI model. Lentiviral vectors overexpressing miR-6722-3p or empty control vectors were administered via tail vein injection post-surgery. Hematoxylin and eosin (H&E) staining was performed to assess renal histopathological changes, while apoptosis in renal tissues was evaluated using the TUNEL assay. Serum levels of blood urea nitrogen (BUN), creatinine (Cr), and inflammatory cytokines (IL-1β and TNF-α) were measured by a biochemical instrument and ELISA, respectively. The mRNA and protein expression levels of CHI3L1, TLR4, and NF-κB p65 were analyzed using quantitative real-time PCR (qRT-PCR) and Western blotting.

Results

Sepsis-induced renal injury was characterized by significant histopathological damage, increased serum Cr, BUN, and inflammatory cytokines. Overexpression of miR-6722-3p suppressed inflammatory cytokine secretion, reduced renal cell apoptosis, and ameliorated renal injury. Additionally, miR-6722-3p overexpression downregulated CHI3L1, TLR4, and NF-κB p65 expression at both mRNA and protein levels.

Conclusion

miR-6722-3p exhibits a protective effect against sepsis-associated AKI, potentially through the modulation of CHI3L1 expression. These findings suggest that miR-6722-3p may serve as a promising therapeutic target for sepsis-induced AKI.

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miR-6722-3p通过靶向CHI3L1改善脓毒症诱导的急性肾损伤

目的：急性肾损伤（AKI）是脓毒症的常见并发症，与发病率和死亡率增加有关。最近的研究表明，microRNAs （miRNAs）在AKI的发病机制中起着至关重要的作用。然而，miR-6722-3p在AKI中的具体作用和潜在机制仍然知之甚少。方法采用盲肠结扎穿孔法（CLP）建立脓毒症致AKI模型。术后通过尾静脉注射过表达miR-6722-3p的慢病毒载体或空对照载体。采用苏木精和伊红（H&；E）染色评估肾组织病理学变化，TUNEL法评估肾组织凋亡。分别用生化仪和酶联免疫吸附法测定血清尿素氮（BUN）、肌酐（Cr）和炎症因子（IL-1β和TNF-α）水平。采用实时荧光定量PCR （qRT-PCR）和Western blotting分析各组小鼠CHI3L1、TLR4、NF-κB p65 mRNA和蛋白表达水平。结果脓毒症引起的肾损伤表现为明显的组织病理学损伤，血清Cr、BUN和炎症因子升高。过表达miR-6722-3p抑制炎症细胞因子分泌，减少肾细胞凋亡，改善肾损伤。此外，miR-6722-3p过表达在mRNA和蛋白水平上下调CHI3L1、TLR4和NF-κB p65的表达。结论mir -6722-3p对脓毒症相关AKI具有保护作用，可能通过调节CHI3L1的表达。这些发现表明，miR-6722-3p可能是脓毒症诱导AKI的一个有希望的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.