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

Khanh M. Chau, Abishai Dominic, Eleanor L. Davis, Sivareddy Kotla, Estefani Turcios Berrios, 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

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Traf2 and Nck-interacting kinase (TNIK) is known for its regulatory role in various processes within cancer cells. However, its role within endothelial cells (ECs) has remained relatively unexplored.

METHODS: Leveraging RNA-seq data and Ingenuity Pathway Analysis (IPA), we probed the potential impact of TNIK depletion on ECs.

RESULTS: Examination of RNA-seq data uncovered more than 450 Differentially Expressed Genes (DEGs) in TNIK-depleted ECs, displaying a fold change exceeding 2 with a false discovery rate (FDR) below 0.05. IPA analysis unveiled that TNIK depletion leads to the inhibition of the interferon (IFN) pathway [-log ( p-value) >11], downregulation of IFN-related genes, and inhibition of Hypercytokinemia/Hyperchemokinemia [-log ( p-value) >8]. The validation process encompassed qRT-PCR to evaluate mRNA expression of crucial IFN-related genes, immunoblotting to gauge STAT1 and STAT2 protein levels, and ELISA for the quantification of IFN and cytokine secretion in siTNIK-depleted ECs. These assessments consistently revealed substantial reductions upon TNIK depletion. When transducing HUVECs with replication incompetent E1-E4 deleted adenovirus expressing green fluorescent protein (Ad-GFP), it was demonstrated that TNIK depletion did not affect the uptake of Ad-GFP. Nonetheless, TNIK depletion induced cytopathic effects (CPE) in ECs transduced with wild-type human adenovirus serotype 5 (Ad-WT).

SUMMARY: Our findings suggest that TNIK plays a crucial role in regulating the EC response to virus infections through modulation of the IFN pathway.

Original languageEnglish (US)
Article number1213428
Pages (from-to)1213428
JournalFrontiers in cardiovascular medicine
StatePublished - 2023


  • interferons
  • RNA-Seq
  • STATs
  • TNIK
  • virus infection

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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