Oxidized high-density lipoprotein impairs the function of human renal proximal tubule epithelial cells through CD36

Area of Science:

• Nephrology
• Cell Biology
• Biochemistry

Background:

• Native high-density lipoprotein (HDL) is protective, but oxidized HDL (oxHDL) has detrimental effects in diseases like chronic kidney disease (CKD).
• The precise mechanisms by which oxHDL contributes to CKD progression, particularly in renal tubular cells, are not fully understood.

Purpose of the Study:

• To investigate the effects of oxHDL on human renal proximal tubule epithelial cells (HK-2).
• To elucidate the role of the scavenger receptor CD36 and key signaling pathways (Src, MAPK, NF-κB) in mediating oxHDL-induced renal cell damage.

Main Methods:

• Human renal proximal tubule epithelial cells (HK-2) were treated with varying concentrations of oxHDL.
• CD36 expression was inhibited using small interfering RNA (siRNA) prior to oxHDL stimulation.
• Cellular responses including reactive oxygen species (ROS) production, pro-inflammatory factor expression, apoptosis, migration, and signaling pathway activation (Src, MAPK, NF-κB) were assessed.

Main Results:

• Oxidized HDL dose-dependently increased ROS production, pro-inflammatory factor expression, and apoptosis in HK-2 cells.
• Oxidized HDL reduced the migration ability of HK-2 cells in a dose-dependent manner.
• Activation of Src family kinase, MAPK, and NF-κB pathways was observed following oxHDL stimulation.
• CD36 siRNA significantly attenuated all the adverse effects induced by oxHDL on HK-2 cells.

Conclusions:

• Oxidized HDL promotes inflammation and impairs the function of renal tubular cells.
• The scavenger receptor CD36 plays a critical role in mediating the detrimental effects of oxHDL on kidney cells.
• The Src, MAPK, and NF-κB signaling pathways are key mediators of oxHDL-induced renal cell injury.