Evidence map›Paper›PMID 25796344›Full record

ArticleExperimental and molecular pathology2015

Vascular smooth muscle cells contribute to APOL1-induced podocyte injury in HIV milieu.

Xiqian Lan, Hongxiu Wen, Moin A Saleem, Joanna Mikulak, Ashwani Malhotra, Karl Skorecki, Pravin C Singhal

Open access · greenAbstract read
In one paragraph

Article in Experimental and molecular pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.9field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Frontiers in genetics · 2022
    Article
  6. Arteriosclerosis, thrombosis, and vascular biology · 2021
    Article
  7. Article
  8. Article
  9. APOL1 Kidney Risk Variants Induce Cell DeathJournal of the American Society of Nephrology : JASN · 2019
    Article
  10. APOL1 and kidney cell function.American journal of physiology. Renal physiology · 2019
    Review
  11. Ten years in: APOL1 reaches beyond the kidney.Current opinion in nephrology and hypertension · 2019
    Review
  12. Review
  13. Most ApoL1 Is Secreted by the Liver.Journal of the American Society of Nephrology : JASN · 2017
    Article
  14. APOL1-Mediated Cell Injury Involves Disruption of Conserved Trafficking Processes.Journal of the American Society of Nephrology : JASN · 2017
    Article
  15. Article
  16. APOL1-G0 or APOL1-G2 Transgenic Models Develop Preeclampsia but Not Kidney Disease.Journal of the American Society of Nephrology : JASN · 2016
    Article
  17. Apolipoprotein L1 and Kidney Disease in African Americans.Trends in endocrinology and metabolism: TEM · 2016
    Review
  18. Review
  19. Protein domains of APOL1 and its risk variants.Experimental and molecular pathology · 2015
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 4 countries.

Xiqian LanRenal Molecular Research Laboratory, Feinstein Institute for Medical Research, Department of Medicine, Hofstra North Shore LIJ Medical School, NY, USA.
Hongxiu WenRenal Molecular Research Laboratory, Feinstein Institute for Medical Research, Department of Medicine, Hofstra North Shore LIJ Medical School, NY, USA.
Moin A SaleemRenal Academic Unit, Department of Pediatrics, University of Bristol, Bristol, UK.
Joanna MikulakUnit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Ashwani MalhotraRenal Molecular Research Laboratory, Feinstein Institute for Medical Research, Department of Medicine, Hofstra North Shore LIJ Medical School, NY, USA.
Karl SkoreckiNephrology and Molecular Medicine, Technion Institute of Technology, Rambam Medical Center, Haifa, Israel.
Pravin C SinghalRenal Molecular Research Laboratory, Feinstein Institute for Medical Research, Department of Medicine, Hofstra North Shore LIJ Medical School, NY, USA. Electronic address: psinghal@nshs.edu.
Feinstein Institute for Medical Research · USHumanitas University · ITTechnion – Israel Institute of Technology · ILUniversity of Bristol · GB

Funding

HIV ASSOCIATED NEPHROPATHY IN DRUG ADDICTSR01DA012111 · NIDA · LONG ISLAND JEWISH MEDICAL CENTER · PI SINGHAL, PRAVIN C · 1998 to 2007
$3.6M
p66ShcA in HIV associated NephropathyR01DK083931 · NIDDK · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI SINGHAL, PRAVIN C · 2010 to 2013
$2.5M
Epigenetic factors and HIV-associated NephropathyR01DK098074 · NIDDK · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI SINGHAL, PRAVIN C · 2013 to 2016
$2.5M
Renin Angioensin Aldosterone System in Drub Abuse and HIV-associated NephropathyR01DK084910 · NIDDK · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI SINGHAL, PRAVIN C · 2010 to 2014
$1.7M
NIDA NIH HHS R01 DA012111NIDDK NIH HHS R01 DK083931NIDDK NIH HHS R01 DK084910NIDDK NIH HHS R01DK084910NIDDK NIH HHS R01 DK098074NIDDK NIH HHS R01DK 098074
6 · The paper itself

Abstract

Clinical reports have demonstrated that higher rates of non-diabetic glomerulosclerosis in African Americans can be attributed to two coding sequence variants (G1 and G2) in the APOL1 gene; however, the underlying mechanism is still unknown. Kidney biopsy data suggest enhanced expression of APOL1/APOL1 variants (Vs) in smooth muscle cells (SMCs) of renal vasculature. Since APOL1 is a secretory protein of relatively low molecular weight (41kDa), SMCs may be a contributory endocrine/paracrine source of APOL1 wild type (WT)/APOL1Vs in the glomerular capillary perfusate percolating podocytes. In the present study, we tested the hypothesis that an HIV milieu stimulated secretion of APOL1 and its risk variants by arterial SMCs contributes to podocyte injury. Human umbilical artery smooth muscle cells (HSMCs)-treated with conditioned media (CM) of HIV-infected peripheral mononuclear cells (PBMC/HIV-CM), CM of HIV-infected U939 cells, or recombinant IFN-γ displayed enhanced expression of APOL1. Podocytes co-cultured in trans-wells with HSMCs-over expressing APOL1WT showed induction of injury; however, podocytes co-cultured with HSMC-over expressing either APOL1G1 or APOL1G2 showed several folds greater injury when compared to HSMC-over expressing APOL1WT. Conditioned media collected from HSMC-over-expressing APOL1G1/APOL1G2 (HSMC/APOL1G1-CM or HSMC/APOL1G2-CM) also displayed higher percentages of injured podocytes in the form of swollen cells, leaky lysosomes, loss of viability, and enhanced sensitivity to adverse host factors when compared to HSMC/APOL1WT-CM. Notably, HSMC/APOL1WT-CM promoted podocyte injury only at a significantly higher concentrations compared to HSMC/APOL1G1/G2-CM. We conclude that HSMCs could serve as an endocrine/paracrine source of APOL1Vs, which mediate accelerated podocyte injury in HIV milieu.

Indexed as

Apolipoprotein L1ApolipoproteinsCell LineCulture Media, ConditionedHIVHumansLipoproteins, HDLMonocytesMuscle, Smooth, VascularPodocytesAPOL1 protein, humanApolipoprotein L1ApolipoproteinsCulture Media, ConditionedLipoproteins, HDL

Identifiers

PMID25796344
PMCPMC4433601
OpenAlexW2016326492

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.