Inflammation Induces Lipid Deposition in Kidneys by Downregulating Renal PCSK9 in Mice with Adriamycin-Induced Nephropathy.

BACKGROUND Previous studies of human and animal models indicate that inflammation alters lipid metabolism. The pro-protein convertase subtilisin kexin type 9 (PCSK9) plays an important role in lipid metabolism. MATERIAL AND METHODS We examined the effect of inflammation on PCSK9 expression and lipid deposition in the kidneys of mice with Adriamycin-induced nephropathy. RESULTS The results indicated an increased expression of inflammatory cytokines and lipid deposition over 12 weeks. During this time, the expression of PCSK9 and its transcriptional activator (hepatocyte nuclear factor 1alpha, HNF1alpha) decreased, and the expression of the low-density lipoprotein receptor (LDLR) and its transcriptional activator (sterol regulatory element binding protein-2, SREBP-2) increased. Exogenous inflammation appeared to further aggravate this process. CONCLUSIONS Our mouse model of nephropathy suggests that a key step in the inflammation-induced deposition of lipids in the kidneys is the downregulation renal PCSK9 expression.