Evidence map›Paper›PMID 31706246›Full record

ArticleEnvironmental toxicology and pharmacology2020

Microcystin exposure worsens nonalcoholic fatty liver disease associated ectopic glomerular toxicity via NOX-2-MIR21 axis.

Sutapa Sarkar, Firas Alhasson, Diana Kimono, Muayad Albadrani, Ratanesh K Seth, Shuo Xiao, Dwayne E Porter, Geoff I Scott, Bryan Brooks, Mitzi Nagarkatti and 2 more

Open access · greenAbstract read
In one paragraph

Article in Environmental toxicology and pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 21% 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

10 citing papers in PubMed, 20 citations in OpenAlex.

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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

12 authors at 3 institutions in 1 country.

Sutapa SarkarEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, United States; NIEHS Center for Oceans and Human Health on Climate Change Interactions, Department of Environmental Health Sciences, University of South Carolina, United States.
Firas AlhassonEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, United States.
Diana KimonoEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, United States; NIEHS Center for Oceans and Human Health on Climate Change Interactions, Department of Environmental Health Sciences, University of South Carolina, United States.
Muayad AlbadraniEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, United States; NIEHS Center for Oceans and Human Health on Climate Change Interactions, Department of Environmental Health Sciences, University of South Carolina, United States.
Ratanesh K SethEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, United States; NIEHS Center for Oceans and Human Health on Climate Change Interactions, Department of Environmental Health Sciences, University of South Carolina, United States.
Shuo XiaoNIEHS Center for Oceans and Human Health on Climate Change Interactions, Department of Environmental Health Sciences, University of South Carolina, United States.
Dwayne E PorterNIEHS Center for Oceans and Human Health on Climate Change Interactions, Department of Environmental Health Sciences, University of South Carolina, United States.
Geoff I ScottNIEHS Center for Oceans and Human Health on Climate Change Interactions, Department of Environmental Health Sciences, University of South Carolina, United States.
Bryan BrooksDepartment of Environmental Science, Baylor University, United States.
Mitzi NagarkattiPathology, Microbiology and Immunology, University of South Carolina School of Medicine, United States.
Prakash NagarkattiPathology, Microbiology and Immunology, University of South Carolina School of Medicine, United States.
Saurabh ChatterjeeEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, United States; NIEHS Center for Oceans and Human Health on Climate Change Interactions, Department of Environmental Health Sciences, University of South Carolina, United States. Electronic address: schatt@mailbox.sc.edu.
South Carolina Department of Health and Environmental Control · USUniversity of South Carolina · USBaylor University · US

Funding

Targeting early ceramide elevation in pre-symptomatic eczemaP20GM103641 · NIGMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI ENOS, REILLY, NAGARKATTI, PRAKASH S · 2012 to 2023
$20.7M
Use of Resveratrol to treat experimental multiple sclerosisP01AT003961 · NCCIH · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, PRAKASH S · 2007 to 2018
$14.2M
The effects of climate change on the natural attenuation and sedimentary record of harmful algal bloom toxins and microbial signalsP01ES028942 · NIEHS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI CHATTERJEE, SAURABH · 2018 to 2022
$5.7M
Role of natural indoles in experimental autoimmune encephalomyelitisR01AT006888 · NCCIH · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, MITZI · 2011 to 2015
$2.0M
Immunopathological basis of PTSDR01MH094755 · NIMH · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, PRAKASH S · 2011 to 2015
$1.7M
Estrogen-T cell InteractionsR01ES019313 · NIEHS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, MITZI, NAGARKATTI, PRAKASH S · 2010 to 2014
$1.5M
NCCIH NIH HHS P01 AT003961NCCIH NIH HHS R01 AT006888NIEHS NIH HHS P01 ES028942NIEHS NIH HHS R01 ES019313NIGMS NIH HHS P20 GM103641NIMH NIH HHS R01 MH094755
6 · The paper itself

Abstract

NAFLD often results in cardiovascular, intestinal and renal complications. Previous reports from our laboratory highlighted NAFLD induced ectopic inflammatory manifestations in the kidney that gave rise to glomerular inflammation. Extending our studies, we hypothesized that existing inflammatory conditions in NAFLD could make the kidneys more susceptible to environmental toxicity. Our results showed that exposure of Microcystin-LR (MC) in NAFLD mice caused a marked increase in cellular scarring with a concomitant increase in mesangial cell activation as observed by increased α-SMA in the extracellular matrix surrounding the glomeruli. Renal tissue surrounding the glomeruli also showed increased NOX2 activation as shown by greater co-localization of p47 Phox and its membrane component gp91Phox both in the mesangial cell and surrounding tissue. Mechanistically, mesangial cells incubated with apocynin, nitrone spin trap DMPO and miR21 inhibitor showed significantly decreased α-SMA, miR21 levels and proinflammatory cytokine release in the supernatant. In parallel, mice lacking miR21, known to be activated by NOX2, when exposed to MC in NAFLD showed decreased mesangial cell activation. Strikingly, phenyl boronic acid incubated cells that were exposed to MC showed significantly decreased mesangial cell activation showing that peroxynitrite might be the major reactive species involved in mediation of the activation process, release of proinflammatory micro RNAs and cytokines that are crucial for renal toxicity. Thus, in conclusion, MC exposure causes NOX2 activation that leads to mesangial cell activation and toxicity via release of peroxynitrite that also represses PTEN by the upregulation of miR21 thus amplifying the toxicity.

Indexed as

Non-alcoholic Fatty Liver DiseaseAnimalsInflammationKidneyKidney DiseasesMiceMicrocystinsMicroRNAsSignal TransductionWater Pollutants, ChemicalMicrocystinsMicroRNAsMIRN21 microRNA, mouseWater Pollutants, ChemicalJAK/STATLeptinMesangial cellsmiR21NADPHNAFLDNOX-2Oxidative stress

Identifiers

PMID31706246
PMCPMC7100051
OpenAlexW2980691639

What OpenQuestion holds

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Registered trials

None linked

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.