Objective: To investigate the expression of WTAP, a mA methylase, in a mouse model of renal ischemia-reperfusion (I/R) injury and the effect of WTAP knockdown on biological behavior of renal tubular epithelial cells exposed to I/R injury.
Methods: Sixteen C57BL/6 mice with renal I/R injury or sham operation (=8) were examined for blood urea nitrogen (BUN) and creatinine (Scr) levels to assess renal function, and renal pathologies were observed with HE staining. The expressions of WTAP and FOXO1 proteins in the kidneys of the mice were detected using immunohistochemistry. Human renal tubular epithelial cells (HK-2) were transfected with si-WTAP or si-NC followed by hypoxia-reoxygenation (H/R) exposure, Protein and mRNA expression were assessed by Western blot and qRT-PCR, and changes and changes in cell viability and apoptosis were assessed using CCK8 assay and TUNEL staining, respectively; LDH release level and caspase-3 activity of the cells were measured using commercial assay kits. FOXO1 mA modification sites were predicted using SRAMP website (http://www.cuilab.cn/sramp/), and the interaction between WTAP and FOXO1 mRNA was analyzed with RIP experiment; the level of FOXO1 modified by mA was detected by MeRIP-qPCR.
Results: Compared with sham-operated mice, the mice with renal I/R injury showed significantly increased Scr and BUN levels ( < 0.001) and renal expressions of WTAP mRNA and protein ( < 0.001). In cultured HK-2 cells, H/R exposure significantly decreased the cell viability ( < 0.001) and increased cellular LDH release ( < 0.001) and expressions of WTAP mRNA and protein ( < 0.001). WTAP knockdown obviously reduced the cell damage induced by I/R injury and significantly decreased the mRNA and protein levels of FOXO1 in the cells ( < 0.001). RIP experiment confirmed WTAP binding to FOXO1 mRNA, and inhibition of WTAP expression significantly reduced FOXO1 mA level in HK-2 cells ( < 0.001).
Conclusion: WTAP expression is up-regulated in the kidneys of mice with renal I/R injury and in HK-2 cells with H/R exposure. Inhibition of WTAP alleviates H/R-induced apoptotic damage in HK-2 cells possibly by inhibiting FOXO1 expression.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10774094 | PMC |
http://dx.doi.org/10.12122/j.issn.1673-4254.2023.12.07 | DOI Listing |
Chem Biol Interact
January 2025
Department of Thoracic Surgery, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, PR China; Jiangxi Hospital of China-Japan Friendship Hospital, National Regional Center for Respiratory Medicine, Nanchang 330000, Jiangxi, PR China; Jiangxi Institute of Respiratory Disease, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, Jiangxi, PR China. Electronic address:
Hyperhomocysteinemia (HHcy) is associated with the development and progression of chronic cardiovascular diseases through the deleterious effects of high levels of homocysteine (Hcy) on the cardiovascular system. However, the exact mechanism of action of Hcy on the acute injury of the cardiovascular system following ischemia/reperfusion (I/R) remains unclear. The present study demonstrated that copper mobilization occurs during cardiac I/R, and the interactive toxic effect of Hcy and mobile Cu during cardiac I/R induces necroptosis of cardiac microvascular endothelial cells (CMECs) and thus enhances cardiac dysfunction.
View Article and Find Full Text PDFOper Neurosurg (Hagerstown)
February 2025
Rhoton Neurosurgery and Otolaryngology Surgical Anatomy Program, Mayo Clinic, Rochester , Minnesota , USA.
Background And Objectives: The coexistence of complete carotico-clinoid bridge (CCB), an ossification between the anterior (ACP) and the middle clinoid (MCP), and an interclinoidal osseous bridge (ICB), between the ACP and the posterior clinoid (PCP), represents an uncommonly reported anatomic variant. If not adequately recognized, osseous bridges may complicate open or endoscopic surgery, along with the pneumatization of the ACP, especially when performing anterior or middle clinoidectomies.
Methods: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines, a systematic scoping review was conducted up to June 5, 2023.
Appl Biochem Biotechnol
January 2025
Department of Nephrology, Affiliated Hospital of Youjiang Medical University for Nationalities, 18Th Zhongshan 2Nd Road, Baise, 533000, Guangxi, China.
A growing body of evidence suggests the involvement of long noncoding ribose nucleic acids (lncRNAs) in acute kidney injury (AKI). This study focused on the mechanistic role of lncRNA small nucleolar RNA host gene 12 (SNHG12) in ischemia/reperfusion (I/R)-mediated AKI. A model of hypoxia/reoxygenation (H/R) was created using human kidney cells (HK-2).
View Article and Find Full Text PDFChin Med J (Engl)
January 2025
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Minimal Invasive Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
Background: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI.
View Article and Find Full Text PDFVet Res Forum
December 2024
Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
Testicular ischemia-reperfusion (I/R) injury during testicular torsion is strongly influenced by oxidative stress caused by excessive accumulation of unscavenged reactive oxygen species. This study aimed to investigate the effects of intra-peritoneal administration of Mito-TEMPO (MT) on I/R injury in testicular torsion/detorsion (T/D) in mice. Forty-two male mice were divided into seven groups including 1 control and 6 treatment groups (360° T/D, 720° T/D, 360° T/D + 0.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!