Evidence map›Paper›PMID 32781293›Full record

ArticleComparative biochemistry and physiology. Toxicology & pharmacology : CBP2020

Higher intestinal and circulatory lactate associated NOX2 activation leads to an ectopic fibrotic pathology following microcystin co-exposure in murine fatty liver disease.

Sutapa Sarkar, Punnag Saha, Ratanesh K Seth, Ayan Mondal, Dipro Bose, Diana Kimono, Muayad Albadrani, Avik Mukherjee, Dwayne E Porter, Geoff I Scott and 6 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

9 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

16 authors at 4 institutions in 1 country.

Sutapa SarkarEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, USA.
Punnag SahaEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, USA.
Ratanesh K SethEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, USA.
Ayan MondalEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, USA.
Dipro BoseEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, USA.
Diana KimonoEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, USA.
Muayad AlbadraniEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, USA.
Avik MukherjeeHunt Optics and Imaging Inc, USA.
Dwayne E PorterNIEHS Center for Oceans and Human Health on Climate Change Interactions, Department of Environmental Health Sciences, University of South Carolina, USA.
Geoff I ScottNIEHS Center for Oceans and Human Health on Climate Change Interactions, Department of Environmental Health Sciences, University of South Carolina, USA.
Shuo XiaoNIEHS Center for Oceans and Human Health on Climate Change Interactions, Department of Environmental Health Sciences, University of South Carolina, USA.
Bryan BrooksDepartment of Environmental Science, Baylor University, USA.
John FerryDepartment of Chemistry and Biochemistry, University of South Carolina, USA.
Mitzi NagarkattiPathology, Microbiology and Immunology(,) University of South Carolina School of Medicine, USA.
Prakash NagarkattiPathology, Microbiology and Immunology(,) University of South Carolina School of Medicine, USA.
Saurabh ChatterjeeEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, USA. Electronic address: schatt@mailbox.sc.edu.
University of South Carolina · USSouth Carolina Department of Health and Environmental Control · USNational Institute of Environmental Health Sciences · 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

Clinical studies implicated an increased risk of intestinal fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Our previous studies have shown that microcystin-LR (MC-LR) exposure led to altered gut microbiome and increased abundance of lactate producing bacteria and intestinal inflammation in underlying NAFLD. This led us to further investigate the effects of the MC-LR, a PP2A inhibitor in activating the TGF-β fibrotic pathway in the intestines that might be mediated by increased lactate induced redox enzyme NOX2. Exposure to MC-LR led to higher lactate levels in circulation and in the intestinal content. The higher lactate levels were associated with NOX2 activation in vivo that led to increased Smad2/3-Smad4 co-localization and high alpha-smooth muscle actin (α-SMA) immunoreactivity in the intestines. Mechanistically, primary mouse intestinal epithelial cells treated with lactate and MC-LR separately led to higher NOX2 activation, phosphorylation of TGFβR1 receptor and subsequent Smad 2/3-Smad4 co-localization inhibitable by apocynin (NOX2 inhibitor), FBA (a peroxynitrite scavenger) and DMPO (a nitrone spin trap), catalase and superoxide dismutase. Inhibition of NOX2-induced redox signaling also showed a significant decrease in collagen protein thus suggesting a strong redox signaling induced activation of an ectopic fibrotic manifestation in the intestines. In conclusion, the present study provides mechanistic insight into the role of microcystin in dysbiosis-linked lactate production and subsequently advances our knowledge in lactate-induced NOX2 exacerbation of the cell differentiation and fibrosis in the NAFLD intestines.

Indexed as

AnimalsCell LineEnzyme InhibitorsFibrosisIntestinal MucosaIntestinesLactic AcidMaleMiceMice, Inbred C57BLMice, KnockoutMicrocystinsNADPH Oxidase 2Non-alcoholic Fatty Liver DiseasePhosphorylationCybb protein, mouseEnzyme InhibitorsLactic AcidmicrocystinMicrocystinsNADPH Oxidase 2DysbiosisFibrosisLactateMC-LRNAFLDNOX2PeroxynitritePP2A inhibitor

Identifiers

PMID32781293
PMCPMC7541568
OpenAlexW3048363687

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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.