The ACE2 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-HEP-1 cell line, engineered to disrupt the human ACE2 gene. This heterogeneous pool of gene-edited cells provides a loss-of-function model suitable for studying ACE2-dependent processes without clonal isolation.
The SK-HEP-1 host cell line is a human hepatic adenocarcinoma line established from patient ascites, exhibiting a mixed endothelial and epithelial phenotype. This unique background supports research into tumor biology, metastasis, and the interplay between epithelial and mesenchymal features, offering a relevant context for cancer cell signaling studies.
ACE2 is a carboxypeptidase that counterbalances the renin-angiotensin system by hydrolyzing angiotensin II into angiotensin-(1-7), which subsequently activates the Mas receptor to elicit vasodilatory, anti-inflammatory, and antifibrotic responses. This enzymatic function opposes the ACE?CAng II?CAT1R axis, maintaining cardiorenal homeostasis. ACE2 also acts as the primary receptor for SARS-CoV and SARS-CoV-2, with the viral spike protein directly binding to its extracellular domain. Upstream regulators of ACE2 include interferon signaling, IL-4, IL-13, angiotensin II, and transcriptional drivers such as HNF1??, GATA4, and FoxA2, while ADAM17 proteolytically sheds ACE2 from the membrane. The amino acid transporter B0AT1 (SLC6A19) is a key interaction partner that stabilizes ACE2 at the cell surface. Downstream, angiotensin-(1-7) promotes nitric oxide release and anti-inflammatory signals, and influences cellular processes via the Mas receptor. Important pathway components encompass renin, angiotensinogen, ACE, angiotensin II, AT1R, ACE2, Ang-(1-7), and the Mas receptor.
In the SK-HEP-1 hepatic adenocarcinoma background, which features a mixed endothelial/epithelial phenotype, ACE2 knockout provides a physiologically relevant platform to dissect RAS equilibrium and viral susceptibility. This model is particularly suited for examining how ACE2 deficiency alters cancer cell behavior, including proliferation, migration, and response to angiotensin peptides. The dual endothelial/epithelial nature also allows investigation of SARS-CoV-2 entry in a non-pulmonary epithelial-like malignancy, offering insights into tissue-specific infectivity mechanisms and host cell dependencies.
This polyclonal knockout cell population supports a broad array of analytical methods, including western blotting, RT-qPCR, immunofluorescence, and flow cytometry for confirmatory profiling, pseudovirus entry assays to evaluate viral uptake, Ang-(1-7) ELISA and ACE2 enzymatic activity measurements to assess RAS modulation, and co-immunoprecipitation for studying interactions with the spike protein or B0AT1. Key research applications include COVID-19 pathogenesis modeling, hypertension and cardiovascular disease studies, diabetic nephropathy research, and the development of antiviral therapeutics. For technical inquiries or further information, please contact Ascent Research.
