Cited by 104Connective Tissue Growth Factor ResearchChronic Kidney Disease and DiabetesTGF-β signaling in diseases

Thrombospondin 1 and Its Diverse Roles as a Regulator of Extracellular Matrix in Fibrotic Disease

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Murphy-Ullrich, Joanne E.·2019·Journal of Histochemistry & Cytochemistry

Abstract

Thrombospondin 1 (TSP1) is a matricellular extracellular matrix protein that has diverse roles in regulating cellular processes important for the pathogenesis of fibrotic diseases. We will present evidence for the importance of TSP1 control of latent transforming growth factor beta activation in renal fibrosis with an emphasis on diabetic nephropathy. Other functions of TSP1 that affect renal fibrosis, including regulation of inflammation and capillary density, will be addressed. Emerging roles for TSP1 N-terminal domain regulation of collagen matrix assembly, direct effects of TSP1–collagen binding, and intracellular functions of TSP1 in mediating endoplasmic reticulum stress responses in extracellular matrix remodeling and fibrosis, which could potentially affect renal fibrogenesis, will also be discussed. Finally, we will address possible strategies for targeting TSP1 functions to treat fibrotic renal disease.

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Registry

Crossref · 10.1369/0022155419851103

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182 of 182 references verified0 citation errors · 0 not checkable

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  • CellChat predicted strong incoming SDC4-mediated signals through THBS1, TNXB, TNC, COL4A, and ANGPTL4.

    “CellChat predicted strong incoming SDC4-mediated signals through THBS1, TNXB, TNC, COL4A, and ANGPTL4 (Figure S5J), all of which are involved in ECM regulation.54,55,56”
  • THBS1, TNXB, TNC, COL4A, and ANGPTL4 are involved in ECM regulation.

    “all of which are involved in ECM regulation.54,55,56”

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Authors
Murphy-Ullrich, J. E.
Affiliations
University of Alabama at Birmingham (US)
Corresponding author
Murphy-Ullrich, Joanne E.
Venue
Journal of Histochemistry & Cytochemistry
Published
2019-05-22
Volume
67
Issue
9
Pages
683-699
ISSN
  • 0022-1554 (ISSN-L)
  • 1551-5044
OpenAlex
W2946132178
Cited by
104
References
182
Citations by year
2026: 10 · 2025: 23 · 2024: 16 · 2023: 14 · 2022: 18 · 2021: 16 · 2020: 6 · 2018: 1
FWCI
0.88
Type
journal article
Language
en
Open access
Locations
  • Journal of Histochemistry & Cytochemistry (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • national institutes of health (NIH grants 1R01 CA175012 and 1R01 EY027924)
  • university of alabama at birmingham (Alabama Drug Discovery Alliance)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
thrombospondin-1, extracellular matrix, renal fibrosis, diabetic nephropathy, latent TGF-beta activation, matricellular proteins, inflammation, capillary density, endoplasmic reticulum stress, extracellular matrix remodeling
MeSH terms
Animals, Collagen, Diabetic Nephropathies, Extracellular Matrix, Fibrosis, Humans, Kidney, Transforming Growth Factor beta, Thrombospondin 1, Renal Insufficiency, Chronic

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