Cited by 264TGF-β signaling in diseasesLiver physiology and pathologySystemic Sclerosis and Related Diseases

Increased PDGFRα Activation Disrupts Connective Tissue Development and Drives Systemic Fibrosis

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Olson, Lorin E., Soriano, Philippe·2009·Developmental Cell

Abstract

PDGF signaling regulates the development of mesenchymal cell types in the embryo and in the adult, but the role of receptor activation in tissue homeostasis has not been investigated. We have generated conditional knockin mice with mutations in PDGFRalpha that drive increased kinase activity under the control of the endogenous PDGFRalpha promoter. In embryos, increased PDGFRalpha signaling leads to hyperplasia of stromal fibroblasts, which disturbs normal smooth muscle tissue in radially patterned organs. In adult mice, elevated PDGFRalpha signaling also increases connective tissue growth, leading to a progressive fibrosis phenotype in multiple organs. Increased PDGFRalpha signaling in an Ink4a/Arf-deficient genetic background leads to accelerated fibrosis, suggesting a new role for tumor suppressors in attenuating fibrotic diseases. These results highlight the role of PDGFRalpha in normal connective tissue development and homeostasis and demonstrate a pivotal role for PDGFRalpha signaling in systemic fibrosis diseases.

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Authors
Olson, L. E., & Soriano, P.
Affiliations
Fred Hutch Cancer Center (US)
Corresponding author
Soriano, Philippe
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2009-02
Volume
16
Issue
2
Pages
303-313
ISSN
1534-5807 (ISSN-L)
OpenAlex
W2031131470
Cited by
264
References
45
Citations by year
2026: 10 · 2025: 8 · 2024: 7 · 2023: 13 · 2022: 17 · 2021: 27 · 2020: 22 · 2019: 18 · 2018: 12 · 2017: 30 · 2016: 21 · 2015: 25 · 2014: 13 · 2013: 13 · 2012: 10
FWCI
3.75
Type
journal article
Language
en
Open access
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Cancer Society (R37HD25326, RO1HD24875)
  • National Institute of Child Health and Human Development
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
Keywords
PDGFRA, PDGF signaling, connective tissue formation, systemic fibrosis, smooth muscle development, tissue homeostasis, tumor suppressor, kinase activity
MeSH terms
Animals, Connective Tissue, Female, Fibroblasts, Fibrosis, Homeostasis, Lung, Mice, Transgenic, Models, Biological, Mutation, Phenotype, Signal Transduction, Receptor, Platelet-Derived Growth Factor alpha, Cell Proliferation, Mice

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