mmu_circ_0000684/hsa_circ_0067098 mediates renal tubular epithelial cells apoptosis to ischemia-reperfusion-induced acute kidney injury by targeting the mmu_miR_671-5p/ARID3B axis

IF 3.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics Pub Date : 2026-02-01 Epub Date: 2025-11-29 DOI:10.1016/j.abb.2025.110679

Ben Yang , Qiang Zheng , Yan Pu , Yingying Hu , Dongshan Zhang

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Abstract

Objective

This investigation sought to explore the possible role of mmu_circ_0000684 and its homolog hsa_circ_0067098 in the evolution of ischemia-reperfusion-induced acute kidney injury (AKI), with an emphasis on their viability as therapeutic targets.

Method

A model was constructed employing Boston University mouse proximal tubule (BUMPT) cells, human renal tubular epithelial (HK-2) cells, and murine kidney tissue. The mmu_circ_0000684, miR-671-5p, and ARID3B mRNA levels, along with their corresponding protein expression, underwent quantification via real-time quantitative polymerase chain reaction and Western blot. A comprehensive examination of the biological roles and signaling cascade of mmu_circ_0000684 and hsa_circ_0067098 was executed utilizing bioinformatics prediction, luciferase reporter assays, fluorescence in situ hybridization, flow cytometry, hematoxylin and eosin staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining.

Results

Ischemic stress was observed to induce mmu_circ_0000684 expression. Functionally, mmu_circ_0000684 was implicated in promoting BUMPT cell apoptosis as a consequence of ischemia-reperfusion injury. Mechanistically, mmu_circ_0000684 acted as a molecular sponge for miR-671-5p, thereby facilitating the upregulation of ARID3B, which in turn contributed to apoptosis induction. Moreover, silencing mmu_circ_0000684 markedly mitigated ischemia-triggered AKI via modulation of the miR-671-5p/ARID3B axis. Notably, hsa_circ_0067098, the homolog of mmu_circ_0000684, exhibited an analogous regulatory role in HK-2 cells.

Conclusion

The mmu_circ_0000684, hsa_circ_0067098/miR-671-5p/ARID3B signaling cascade emerges as an essential mechanism during ischemic AKI progression. Consequently, hsa_circ_0067098 represents a promising therapeutic candidate for addressing ischemic AKI.

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mmu_circ_0000684/hsa_circ_0067098通过靶向mmu_miR_671-5p/ARID3B轴介导肾小管上皮细胞凋亡至缺血再灌注诱导的急性肾损伤

目的：本研究旨在探讨mmu_circ_00684及其同源基因hsa_circ_0067098在缺血-再灌注诱导的急性肾损伤（AKI）进化中的可能作用，并重点研究它们作为治疗靶点的可行性。方法：采用波士顿大学小鼠近端小管细胞（BUMPT）、人肾小管上皮细胞（HK-2）和小鼠肾组织构建模型。mmu_circ_0000684、miR-671-5p和ARID3B mRNA水平及其相应的蛋白表达通过实时定量聚合酶链反应和Western blot进行定量。利用生物信息学预测、荧光素酶报告基因测定、荧光原位杂交、流式细胞术、苏木精和伊红染色、末端脱氧核苷酸转移酶dUTP标记染色，对mmu_circ_0000684和hsa_circ_0067098的生物学作用和信号级联进行了全面的研究。结果：缺血应激诱导mmu_circ_0000684表达。功能上，mmu_circ_0000684参与促进BUMPT细胞因缺血再灌注损伤而凋亡。在机制上，mmu_circ_0000684作为miR-671-5p的分子海绵，从而促进ARID3B的上调，进而促进细胞凋亡的诱导。此外，沉默mmu_circ_0000684可通过调节miR-671-5p/ARID3B轴显著减轻缺血触发的AKI。值得注意的是，hsa_circ_0067098， mmu_circ_0000684的同源物，在HK-2细胞中表现出类似的调节作用。结论：mmu_circ_0000684， hsa_circ_0067098/miR-671-5p/ARID3B信号级联是缺血性AKI进展的重要机制。因此，hsa_circ_0067098代表了解决缺血性AKI的有希望的治疗候选者。

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来源期刊

Archives of biochemistry and biophysics 生物-生化与分子生物学

CiteScore

7.40

自引率

0.00%

发文量

245

审稿时长

26 days

期刊介绍： Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics. Research Areas Include: • Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing • Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions • Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.