The ANGPTL4 Knockout HK-2 Cell Line is a CRISPR/Cas9-edited knockout cell line derived from the human HK-2 proximal tubular epithelial cell line, featuring targeted disruption of the ANGPTL4 gene. This product provides a loss-of-function model for studying angiopoietin-like 4, a secreted inhibitor of lipoprotein lipase (LPL), without interference from endogenous ANGPTL4 expression. The cell line is suitable for diverse in vitro functional assays in renal biology and metabolic research.
HK-2 is an immortalized human kidney proximal tubule epithelial cell line derived from normal adult kidney. Proximal tubular cells carry out solute reabsorption and secretion, acid-base regulation, and renal metabolism. HK-2 is a widely used model for nephrotoxicity screening, renal disease investigation, and studies of tubular transport and metabolic function, providing a physiologically relevant host for exploring lipid handling and metabolic stress.
ANGPTL4 encodes a secreted glycoprotein that primarily inhibits LPL activity, thereby regulating plasma triglycerides and cellular fatty acid uptake. Its expression is upregulated by PPAR??, PPAR??, glucocorticoids, HIF-1??, TNF-??, and IL-1??, and by fasting/insulin signaling. ANGPTL4 interacts with LPL, integrins ??5??1, and heparan sulfate proteoglycans via its C-terminal fibrinogen-like domain. Downstream, it suppresses LPL-mediated hydrolysis, reduces free fatty acid uptake, and modulates integrin-dependent ITG??5??1-FAK signaling and the PI3K/Akt pathway. Representative components include VLDL, chylomicrons, CD36, FATP, and the PPAR??-RXR-PGC1?? complex.
In HK-2 cells, ANGPTL4 knockout removes the endogenous LPL inhibitor, potentially enhancing local lipid uptake and altering cellular energy metabolism and inflammatory signaling. This model enables dissection of ANGPTL4’s role in proximal tubular lipid handling and responses to injury, including processes relevant to diabetic nephropathy, obesity-related kidney injury, and acute kidney injury.
This cell line supports mechanistic studies of renal lipid metabolism, screening of PPAR agonists, and investigation of tubular responses to metabolic stress. Typical assays include western blotting, RT-qPCR, LPL activity measurements, BODIPY-labeled fatty acid uptake, cell migration, apoptosis (Annexin V), immunofluorescence for integrins, and RNA-seq. It is useful for evaluating ANGPTL4 as a therapeutic target. For further details or tailored applications, please contact Ascent Research.
