Yang Yang , Jing-jing Pan , Xiao-qing Chen , Jia Shi , Mu-zi Wang , Tian-yu Liu , Xiao-guang Zhou
{"title":"CircPICALM promotes neonatal acute kidney injury triggered by hypoxia/reoxygenation via sponging microRNA-204-5p","authors":"Yang Yang , Jing-jing Pan , Xiao-qing Chen , Jia Shi , Mu-zi Wang , Tian-yu Liu , Xiao-guang Zhou","doi":"10.1016/j.bbadis.2025.167795","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>C57BL/6 mice born 7 days were divided into Control group and hypoxia groups (11%O<sub>2</sub> and 8%O<sub>2</sub> 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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167795"},"PeriodicalIF":4.2000,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et biophysica acta. Molecular basis of disease","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0925443925001401","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
CircPICALM promotes neonatal acute kidney injury triggered by hypoxia/reoxygenation via sponging microRNA-204-5p
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.
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.