Increased PDGFRα Activation Disrupts Connective Tissue Development and Drives Systemic Fibrosis
Open accessAbstract
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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The Pdgf pathway is crucial to disease pathogenesis.
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From Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage (2019) · cites this paper as [42]
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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)
- PMC
- PMC2664622
- 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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1663 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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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