The HPX Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-HEP-1 human hepatic sinusoidal endothelial cell line. This product provides a loss-of-function model for the HPX gene, which encodes the plasma glycoprotein hemopexin. The polyclonal format ensures a diverse allelic distribution resulting from CRISPR/Cas9-mediated gene disruption, enabling the study of HPX deficiency in a heterogeneous cell population rather than a single clonal isolate.
SK-HEP-1 cells were originally isolated from the ascites of a patient with liver adenocarcinoma and exhibit an adherent endothelial morphology. They functionally model hepatic sinusoidal endothelial cells, which form the liver sinusoid endothelium and play critical roles in filtration, endocytosis, and maintenance of liver homeostasis. This cellular context provides a physiologically relevant platform for investigating hemopexin-mediated pathways, as hepatic endothelium is a primary site of heme?Chemopexin complex clearance via receptor-mediated endocytosis.
Hemopexin (HPX) binds free heme with high affinity, forming a complex that is recognized by the LRP1/CD91 receptor. Upstream regulators such as IL-6, TNF-alpha, and heme, acting through STAT3 and C/EBP transcription factors, control HPX expression. Upon internalization, heme is degraded by heme oxygenase-1 (HO-1), releasing iron and inducing cytoprotective genes. Iron export is mediated by ferroportin, while ferritin stores excess iron. This pathway mitigates oxidative stress by limiting free heme-driven reactive oxygen species (ROS) production, thus HPX is a critical node in heme scavenging, iron homeostasis, and the acute phase response.
Disruption of HPX in SK-HEP-1 cells creates a valuable in vitro model to dissect heme?CHPX?CLRP1 endocytic signaling and its downstream effects on oxidative stress and iron metabolism in hepatic endothelium. The polyclonal knockout population enables investigation of loss-of-function phenotypes without clonal artifacts, reflecting heterogeneous gene disruption patterns. This model is particularly relevant for studying diseases where heme toxicity and impaired scavenging contribute to pathology, such as hemolytic anemia, atherosclerosis, acute kidney injury, and neurodegeneration.
Researchers can employ these cells in heme uptake assays, cell viability assessments under heme stress, western blotting for HO-1 and ferritin, ROS detection, iron quantification, and endothelial barrier permeability assays. RT-qPCR for inflammatory cytokines can profile the acute phase response. The knockout model supports studies on heme scavenging therapy evaluation and iron homeostasis. For further details, please contact Ascent Research.
