Abstract
Acute kidney injury (AKI) is a severe and frequently observed condition associated with high morbidity and mortality. The molecular mechanisms underlying AKI have not been elucidated due to the complexity of the pathophysiological processes. Thus, we investigated the key biological molecules contributing to AKI based on the transcriptome profile. We analyzed the RNA sequencing data from 39 native human renal biopsy samples and 9 reference nephrectomies from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and Gene Ontology (GO) analysis revealed that various GO terms were dysregulated in AKI. Gene set enrichment analysis (GSEA) highlighted dysregulated pathways, including “DNA replication,” “chemokine signaling pathway,” and “metabolic pathways.” Furthermore, the protein-to-protein interaction (PPI) networks of the DEGs were constructed, and the hub genes were identified using Cytoscape. Moreover, weighted gene co-expression network analysis (WGCNA) was performed to validate the DEGs in AKI-related modules. Subsequently, the upregulated hub genes STUB1, SOCS1, and VHL were validated as upregulated in human AKI and a mouse cisplatin-induced AKI model. Moreover, the biological functions of STUB1 were investigated in renal tubular epithelial cells. Cisplatin treatment increased STUB1 expression in a dose-dependent manner at both the mRNA and protein levels. Knockdown of STUB1 by siRNA increased the expression of proapoptotic Bax and cleaved caspase-3 while decreasing antiapoptotic Bcl-2. In addition, silencing STUB1 increased the apoptosis of HK-2 cells and the proinflammatory cytokine production of IL6, TNFα, and IL1β induced by cisplatin. These results indicated that STUB1 may contribute to the initiation and progression of AKI by inducing renal tubular epithelial cell apoptosis and renal inflammation.
Highlights
Acute kidney injury is characterized by the abrupt onset of abnormal kidney functions
According to a threshold of fold change greater than 2 and p value less than 0.05, a total of 1,160 significant differentially expressed genes (DEGs) were identified compared to the REF group, including the 747 upregulated and 413 downregulated genes
We investigated whether the STUB1, SOCS1, and von Hippel–Lindau (VHL) genes were upregulated in the mouse Acute kidney injury (AKI) model
Summary
Acute kidney injury is characterized by the abrupt onset of abnormal kidney functions. As a common clinical symptom, AKI is defined by a surge in serum creatinine and a rapid decrease in urine output within a short time (Khwaja, 2012). The incidence of AKI has steadily increased. The incidence of AKI in ordinary hospitalized patients is 5–20%, and the incidence in intensive care units is as high as 30–60% (Jacob et al, 2020). AKI is induced by various conditions, such as suffering from ischemia, toxic agents, decreased kidney perfusion, and inflammation (Ali et al, 2007). Many factors are known to be responsible for AKI, the underlying molecular mechanisms are still poorly understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
