Evidence mapPaperPMID 29996896Full record

ArticleArthritis research & therapy2018

Adipocyte-specific Repression of PPAR-gamma by NCoR Contributes to Scleroderma Skin Fibrosis.

Benjamin Korman, Roberta Goncalves Marangoni, Gabriel Lord, Jerrold Olefsky, Warren Tourtellotte, John Varga

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. [Research progress on cellular metabolic reprogramming in skin fibrosis].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Adiponectin Deregulation in Systemic Autoimmune Rheumatic Diseases.International journal of molecular sciences · 2021
    Review
  16. Review
  17. Article
  18. Review
  19. Metabolic Dysregulation in Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2020
    Review
  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

6 authors at 3 institutions in 1 country.

Benjamin KormanNorthwestern Scleroderma Program, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. benjamin_korman@urmc.rochester.edu.ORCID 0000-0002-4873-2628
Roberta Goncalves MarangoniNorthwestern Scleroderma Program, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Gabriel LordNorthwestern Scleroderma Program, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Jerrold OlefskyDivision of Endocrinology, University of California, San Diego, La Jolla, CA, USA.
Warren TourtellotteDepartment of Pathology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
John VargaNorthwestern Scleroderma Program, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Northwestern University · USCedars-Sinai Medical Center · USUniversity of California San Diego · US

Funding

REGULATION OF COLLAGEN GENE EXPRESSION BY TGF-BETAR01AR042309 · UNIVERSITY OF ILLINOIS AT CHICAGO · 1994 to 2005
$1.6M
Resource CoreP30AR072579 · NORTHWESTERN UNIVERSITY · 2025 to 2025
$689k
IMMEDIATE EARLY GENE REGULATED DEVELOPMENT/PLASTICITYK02NS046468 · NORTHWESTERN UNIVERSITY · 2005 to 2005
$136k
NCRR NIH HHS K26 RR026099NIAMS NIH HHS K08 AR070285NIAMS NIH HHS K08-AR070285-01NIAMS NIH HHS P30 AR072579NIAMS NIH HHS R01 AR042309NIAMS NIH HHS R01 AR42309NIAMS NIH HHS R03 AR066343NICHD NIH HHS K12 HD055884NIH HHS K26 OD010945NINDS NIH HHS K02 NS046468
6 · The paper itself

Abstract

backgroundA pivotal role for adipose tissue homeostasis in systemic sclerosis (SSc) skin fibrosis is increasingly recognized. The nuclear receptor PPAR-γ is the master regulator of adipogenesis. Peroxisome proliferator activated receptor-γ (PPAR-γ) has antifibrotic effects by blocking transforming growth factor-β (TGF-β) and is dysregulated in SSc. To unravel the impact of dysregulated PPAR-γ in SSc, we focused on nuclear corepressor (NCoR), which negatively regulates PPAR-γ activity and suppresses adipogenesis.

methodsAn NCoR-regulated gene signature was measured in the SSc skin transcriptome. Experimental skin fibrosis was examined in mice with adipocyte-specific NCoR ablation.

resultsSSc skin biopsies demonstrated deregulated NCoR signaling. A 43-gene NCoR gene signature showed strong positive correlation with PPAR-γ signaling (R = 0.919, p < 0.0001), whereas negative correlations with TGF-β signaling (R = - 0.796, p < 0.0001) and the modified Rodnan skin score (R = - 0.49, p = 0.004) were found. Mice with adipocyte-specific NCoR ablation demonstrated significant protection from experimental skin fibrosis and inflammation. The protective effects were mediated primarily through endogenous PPAR-γ.

conclusionsOur results implicate, for the first time, to our knowledge, deregulated NCoR/PPAR-γ pathways in SSc, and they support a role of adipocyte modulation of skin fibrosis. Pharmacologic restoration of NCoR/PPAR-γ signaling may represent a novel strategy to control skin fibrosis in SSc.

Indexed as

AdipocytesAdultAgedAnimalsFemaleFibrosisHumansMaleMiceMice, Inbred C57BLMiddle AgedNuclear Receptor Co-Repressor 1PPAR gammaScleroderma, SystemicSkinNuclear Receptor Co-Repressor 1PPAR gammaAdipocyteAdipogenesisFibrogenesisNCoRPPAR-γSclerodermaSkin fibrosis

Identifiers

PMID29996896
PMCPMC6042240
OpenAlexW2823705647

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.