The STING1 Knockout HK-2 Cell Line is a CRISPR/Cas9-edited human knockout cell line featuring targeted disruption of the STING1 (TMEM173) gene. This loss-of-function model enables researchers to interrogate STING1-dependent signaling in a defined human renal proximal tubule epithelial background. The cell line is generated using CRISPR/Cas9-mediated gene disruption, resulting in abrogation of STING1 protein expression. It provides a stable and reproducible system for studying innate immune pathways, particularly the cGAS-STING axis, without the confounding effects of residual STING activity.
The parental HK-2 cell line is an immortalized human kidney proximal tubule epithelial line derived from normal adult renal tissue. It retains morphological and functional features of proximal tubular epithelia, including polarity and transport capacity, serving as a standard model for renal physiology, drug handling, and nephrotoxicity. HK-2 cells also express innate immune sensors and can produce inflammatory responses, making them suitable for studying tubular immune signaling. The STING1 knockout derivative enables focused analysis of nucleic acid sensing pathways in this context.
STING1, encoded by TMEM173, is an endoplasmic reticulum-resident adaptor that detects cytosolic cyclic dinucleotides, primarily 2’3′-cGAMP produced by cGAS upon sensing double-stranded DNA. Ligand binding induces STING1 trafficking via SEC24C to the Golgi, where it recruits TBK1 to phosphorylate IRF3 and activate NF-kappaB. Phosphorylated IRF3 dimerizes and drives transcription of type I interferons (IFNB1) and interferon-stimulated genes (ISG15, CXCL10). Upstream regulators include TREX1, which degrades cytosolic DNA, and ULK1, which attenuates STING activity. STING1 also interacts with STIM1 and can engage in crosstalk with RIG-I pathways.
In renal proximal tubule cells, STING1 signaling contributes to inflammation triggered by mitochondrial DNA release during stress, relevant to acute kidney injury and chronic kidney disease. The knockout line enables dissection of cell-intrinsic STING roles in interferon production, immune cell recruitment, and tubular damage, and supports studies on STING1-mediated autophagy, senescence, and metabolic regulation. It also provides a platform for evaluating STING-targeted therapies in a kidney-relevant context.
Applications encompass innate immunity research, cGAS-STING pathway analysis, host-pathogen interactions, cancer immunotherapy, and autoinflammatory disease modeling including SAVI. In renal studies, it facilitates investigation of STING-dependent tubular inflammation and drug screening. Key assays include Western blotting for STING/TBK1/phospho-IRF3, RT-qPCR for IFNB1/CXCL10, immunofluorescence for STING translocation, cGAMP-induced IFN-?? luciferase reporter, and co-immunoprecipitation of STING-TBK1. For further information, contact Ascent Research.
