TNIK regulation of interferon signaling and endothelial cell response to virus infection

• DOI: 10.3389/fcvm.2023.1213428
• Publication Date: 2024-01-09T04:36:34Z
• Authors: Khanh M. Chau; Abishai Dominic; Eleanor L. Davis; Sivareddy Kotla; Estefani Turcios ...; Arsany Fahim; Ashwin Arunesh; Shengyu Li; Dongyu Zhao; Kaifu Chen; Alan R. Davis; Minh T. H. Nguyen; Yongxing Wang; Scott E. Evans; Guangyu Wang; John P. Cooke; Jun-ichi Abe; David P. Huston; Nhat-Tu Le
• Keywords: 0303 health sciences; Medical Sciences; Bioinformatics; Cardiology; 500; 610; Diseases; Infectious Disease; Cardiovascular Medicine; Biomedical Informatics; interferons; STATs; 03 medical and health sciences; Cardiovascular Diseases; RC666-701; Internal Medicine; Medical Specialties; Medicine and Health Sciences; virus infection; Diseases of the circulatory (Cardiovascular) system; RNA-Seq; TNIK

Background Traf2 and Nck-interacting kinase (TNIK) is known for its regulatory role in various processes within cancer cells. However, endothelial cells (ECs) has remained relatively unexplored. Methods Leveraging RNA-seq data Ingenuity Pathway Analysis (IPA), we probed the potential impact of TNIK depletion on ECs. Results Examination uncovered more than 450 Differentially Expressed Genes (DEGs) TNIK-depleted ECs, displaying a fold change exceeding 2 with false discovery rate (FDR) below 0.05. IPA analysis unveiled that leads to inhibition interferon (IFN) pathway [-log ( p -value) >11], downregulation IFN-related genes, Hypercytokinemia/Hyperchemokinemia >8]. The validation process encompassed qRT-PCR evaluate mRNA expression crucial immunoblotting gauge STAT1 STAT2 protein levels, ELISA quantification IFN cytokine secretion siTNIK-depleted These assessments consistently revealed substantial reductions upon depletion. When transducing HUVECs replication incompetent E1-E4 deleted adenovirus expressing green fluorescent (Ad-GFP), it was demonstrated did not affect uptake Ad-GFP. Nonetheless, induced cytopathic effects (CPE) ECs transduced wild-type human serotype 5 (Ad-WT). Summary Our findings suggest plays regulating EC response virus infections through modulation pathway.