CircPICALM promotes neonatal acute kidney injury triggered by hypoxia/reoxygenation via sponging microRNA-204-5p

IF 4.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-03-12 DOI:10.1016/j.bbadis.2025.167795
Yang Yang , Jing-jing Pan , Xiao-qing Chen , Jia Shi , Mu-zi Wang , Tian-yu Liu , Xiao-guang Zhou
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Abstract

Background

Circular RNAs (circRNAs) have been documented to regulate neonatal acute kidney injury (AKI). Based on previous RNA-sequence findings, circPICALM exhibited significantly disparate expression between AKI newborns and Controls. This study aimed to provide further insights into the regulatory mechanism of circPICALM in neonatal AKI.

Methods

C57BL/6 mice born 7 days were divided into Control group and hypoxia groups (11%O2 and 8%O2 groups). Human tubule epithelial cells (HK-2) were stimulated with hypoxia/reoxygenation (H/R) to establish an AKI cell model. Through overexpression and knockdown techniques, the regulatory role of circPICALM in H/R-induced kidney injury was explored. Inflammatory cytokines, cell apoptosis, and oxidative stress were also detected to confirm the regulatory function of circPICALM in neonatal AKI.

Results

RT-qPCR confirmed that circPICALM was highly expressed in the serum of AKI newborns, neonatal I/R mice and H/R-treated HK-2 cells. Functionally, circPICALM exacerbated H/R-induced HK-2 cell injury by aggravating apoptosis and mitochondrial oxidative stress, increasing the expression of inflammatory factors, including IL-6, IL-1β, and TNF-α. Conversely, inhibition of circPICALM alleviated H/R injury in the HK-2 cell line. The interaction between circPICALM and miR-204-5p was validated through RNA immunoprecipitation and luciferase assay. Finally, circPICALM functioned as a molecular sponge of miR-204-5p and promoted the upregulation of downstream IL-1β expression.

Conclusion

CircPICALM plays a critical role in H/R-induced neonatal AKI by sponging miR-204-5p and then activating the downstream IL-1β signaling axis. The inhibition of circPICALM and subsequent suppression of pro-inflammatory factors could serve as a promising biomarker and therapeutic target for early intervention in neonatal AKI.

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背景有文献记载,环状 RNA(circRNA)可调控新生儿急性肾损伤(AKI)。根据以前的 RNA 序列发现,circPICALM 在 AKI 新生儿和对照组之间的表达有显著差异。方法将出生 7 天的 C57BL/6 小鼠分为对照组和缺氧组(11%O2 组和 8%O2 组)。用缺氧/再氧合(H/R)刺激人肾小管上皮细胞(HK-2),建立 AKI 细胞模型。通过过表达和基因敲除技术,探讨了circPICALM在H/R诱导的肾损伤中的调控作用。结果RT-qPCR证实,circPICALM在AKI新生儿、新生I/R小鼠和H/R处理的HK-2细胞血清中高表达。从功能上讲,circPICALM 通过加剧细胞凋亡和线粒体氧化应激,增加炎症因子(包括 IL-6、IL-1β 和 TNF-α)的表达,加剧了 H/R 诱导的 HK-2 细胞损伤。相反,抑制 circPICALM 可减轻 HK-2 细胞系的 H/R 损伤。通过 RNA 免疫沉淀和荧光素酶实验验证了 circPICALM 与 miR-204-5p 之间的相互作用。最后,circPICALM 作为 miR-204-5p 的分子海绵,促进了下游 IL-1β 表达的上调。抑制 circPICALM 并随之抑制促炎因子可作为早期干预新生儿 AKI 的一种有前景的生物标记物和治疗靶点。
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来源期刊
CiteScore
12.30
自引率
0.00%
发文量
218
审稿时长
32 days
期刊介绍: BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.
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