APOL1-G0 protects podocytes in a mouse model of HIV-associated nephropathy.
Abstract
African polymorphisms in the gene for Apolipoprotein L1 (APOL1) confer a survival
advantage against lethal trypanosomiasis but also an increased risk for several chronic
kidney diseases (CKD) including HIV-associated nephropathy (HIVAN). APOL1 is expressed
in renal cells, however, the pathogenic events that lead to renal cell damage and
kidney disease are not fully understood. The podocyte function of APOL1-G0 versus
APOL1-G2 in the setting of a known disease stressor was assessed using transgenic
mouse models. Transgene expression, survival, renal pathology and function, and podocyte
density were assessed in an intercross of a mouse model of HIVAN (Tg26) with two mouse
models that express either APOL1-G0 or APOL1-G2 in podocytes. Mice that expressed
HIV genes developed heavy proteinuria and glomerulosclerosis, and had significant
losses in podocyte numbers and reductions in podocyte densities. Mice that co-expressed
APOL1-G0 and HIV had preserved podocyte numbers and densities, with fewer morphologic
manifestations typical of HIVAN pathology. Podocyte losses and pathology in mice co-expressing
APOL1-G2 and HIV were not significantly different from mice expressing only HIV. Podocyte
hypertrophy, a known compensatory event to stress, was increased in the mice co-expressing
HIV and APOL1-G0, but absent in the mice co-expressing HIV and APOL1-G2. Mortality
and renal function tests were not significantly different between groups. APOL1-G0
expressed in podocytes may have a protective function against podocyte loss or injury
when exposed to an environmental stressor. This was absent with APOL1-G2 expression,
suggesting APOL1-G2 may have lost this protective function.
Type
Journal articleSubject
Kidney GlomerulusAnimals
Mice, Inbred BALB C
Mice, Transgenic
Humans
Mice
AIDS-Associated Nephropathy
Disease Models, Animal
Genetic Predisposition to Disease
Apolipoproteins
Polymorphism, Genetic
Podocytes
Renal Insufficiency, Chronic
Genetic Variation
Transcriptome
Apolipoprotein L1
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https://hdl.handle.net/10161/22302Published Version (Please cite this version)
10.1371/journal.pone.0224408Publication Info
Bruggeman, Leslie A; Wu, Zhenzhen; Luo, Liping; Madhavan, Sethu; Drawz, Paul E; Thomas,
David B; ... Sedor, John R (2019). APOL1-G0 protects podocytes in a mouse model of HIV-associated nephropathy. PloS one, 14(10). pp. e0224408. 10.1371/journal.pone.0224408. Retrieved from https://hdl.handle.net/10161/22302.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Laura Barisoni
Professor of Pathology
David Thomas
Adjunct Professor in the Department of Pathology
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