title: APOL1 localization in normal kidney and nondiabetic kidney disease.
abstract: In patients of African ancestry, genetic variants in APOL1, which encodes apolipoprotein L1, associate with the nondiabetic kidney diseases, focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy (HIVAN), and hypertensive nephropathy. Understanding the renal localization of APOL1 may provide clues that will ultimately help elucidate the mechanisms by which APOL1 variants promote nephropathy. Here, we used immunohistology to examine APOL1 localization in normal human kidney sections and in biopsies demonstrating either FSGS (n = 8) or HIVAN (n = 2). Within normal glomeruli, APOL1 only localized to podocytes. Compared with normal glomeruli, fewer cells stained for APOL1 in FSGS and HIVAN glomeruli, even when expression of the podocyte markers GLEPP1 and synaptopodin appeared normal. APOL1 localized to proximal tubular epithelia in normal kidneys, FSGS, and HIVAN. We detected APOL1 in the arteriolar endothelium of normal and diseased kidney sections. Unexpectedly, in both FSGS and HIVAN but not normal kidneys, the media of medium artery and arterioles contained a subset of α-smooth muscle actin-positive cells that stained for APOL1. Comparing the renal distribution of APOL1 in nondiabetic kidney disease to normal kidney suggests that a previously unrecognized arteriopathy may contribute to disease pathogenesis in patients of African ancestry.
authors: Department of Medicine and the Rammel kamp Center for Education and Research, Metro Health System Campus, Cleveland, Ohio, USA.
authors: Sethu M
authors: SM
authors: Madhavan
authors: John F
authors: JF
authors: O'Toole
authors: Martha
authors: M
authors: Konieczkowski
authors: Santhi
authors: S
authors: Ganesan
authors: Leslie A
authors: LA
authors: Bruggeman
authors: John R
authors: JR
authors: Sedor
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D002461:Cell Line, Transformed; D003920:Diabetes Mellitus / Q000453:epidemiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005923:Glomerulosclerosis, Focal Segmental / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000166:cytology / Q000502:physiology*; D012079:Renal Circulation / Q000502:physiology; D012307:Risk Factors
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL