CoChat
Sign Up
Cited by 243Systemic Sclerosis and Related DiseasesNitric Oxide and Endothelin EffectsTGF-β signaling in diseases

The DOI matches its Crossref record; 32 of the 35 references it cites were found in a registry or an index.

Fibroblast Matrix Gene Expression and Connective Tissue Remodeling: Role of Endothelin-1

Open access
Shi-wen, Xu, Denton, Christopher P., Holmes, Alan M., Black, Carol M., Abraham, David J., Dashwood, Michael R., Bou-Gharios, George, Pearson, Jeremy D.·2001·Journal of Investigative Dermatology
DOI 10.1046/j.1523-1747.2001.01256.x
Open this paper in CoChat — free account

Abstract

This study examines endothelin-induced modulation of extracellular matrix synthesis and remodeling by fibroblasts, and its potential role in the pathogenesis of systemic sclerosis (scleroderma). Endothelin-1 promoted fibroblast synthesis of collagen types I and III, but not fibronectin, by a mechanism dependent upon both ETA and ETB receptors. Conversely, endothelin-1 inhibited both protein expression of matrix metalloproteinase 1 and zymographic activity exclusively via ETA receptors. A dual regulatory role for endothelin-1 in transcriptional regulation was suggested by the ability of endothelin-1 to enhance steady-state levels of collagen mRNA and activate the proalpha2(I) collagen (Col1a2) promoter, but in contrast to reduce matrix metalloproteinase 1 transcript expression and suppress transcription of a human matrix metalloproteinase 1 promoter reporter construct in transient transfection assays. Although endothelin-1 significantly enhanced remodeling of three-dimensional collagen lattices populated by normal fibroblasts, this was not observed for lattices populated by systemic sclerosis fibroblasts. Promotion of matrix remodeling was dependent upon ETA receptor expression and was blocked by specific inhibitors of tyrosine kinases or protein kinase C. Reverse transcriptase polymerase chain reaction, S1 nuclease, and functional cell surface binding studies showed that normal and systemic sclerosis fibroblasts express both ETA and ETB receptors (predominantly ETA), but that ETA receptor mRNA levels and ETA binding sites on fibroblasts cultured from systemic sclerosis skin biopsies are reduced by almost 50%. Endothelin-1 is thus able to induce a fibrogenic phenotype in normal fibroblasts that is similar to that of lesional systemic sclerosis fibroblasts. Moreover, reduced responsiveness to exogenous endothelin-1 in systemic sclerosis suggests that downstream pathways may have already been activated in vivo. These data further implicate dysregulated endothelin-receptor pathways in fibroblasts in the pathogenesis of connective tissue fibrosis.

Overview

Integrity signals

Registry

Crossref · 10.1046/j.1523-1747.2001.01256.x

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Cited by

Sorted by citations

See all 243

Related

See all

Metadata

Authors
Shi-wen, X., Denton, C. P., Holmes, A. M., Black, C. M., Abraham, D. J., Dashwood, M. R., Bou-Gharios, G., & Pearson, J. D.
Affiliations
  • The Royal Free Hospital (GB)
  • King's College London (GB)
Corresponding author
Abraham, David J.
ORCID
Venue
Journal of Investigative Dermatology
Publisher
Elsevier BV
Published
2001-03
Volume
116
Issue
3
Pages
417-425
ISSN
0022-202X (ISSN-L)
DOI
10.1046/j.1523-1747.2001.01256.x
OpenAlex
W2064485592
Cited by
243
References
35
Citations by year
2026: 2 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 10 · 2015: 13 · 2014: 11 · 2013: 12 · 2012: 6
FWCI
5.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Investigative Dermatology (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Sclerosis and Related Diseases
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
endothelin-1, systemic sclerosis, fibroblasts, extracellular matrix remodeling, collagen synthesis, type I collagen, type III collagen, fibronectin, MMP-1, ETA receptor, endothelin B receptor, connective tissue fibrosis, tyrosine kinase inhibitors, protein kinase C
MeSH terms
Cells, Cultured, Collagen, Connective Tissue, Extracellular Matrix, Fibroblasts, Humans, Reference Values, RNA, Messenger, Scleroderma, Systemic, Transcription, Genetic, Gene Expression, Receptors, Endothelin, Endothelin-1, Matrix Metalloproteinase 1, Receptor, Endothelin A, Receptor, Endothelin B

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review