PDGFRα plays a crucial role in connective tissue remodeling
Open accessAbstract
Platelet derived growth factor (PDGF) plays a pivotal role in the remodeling of connective tissues. Emerging data indicate the distinctive role of PDGF receptor-α (PDGFRα) in this process. In the present study, the Pdgfra gene was systemically inactivated in adult mouse (α-KO mouse) and the role of PDGFRα was examined in the subcutaneously implanted sponge matrices. PDGFRα expressed in the fibroblasts of Pdgfra -preserving control mice (Flox mice), was significantly reduced in the sponges in α-KO mice. Neovascularized areas were largely suppressed in the α-KO mice than in the Flox mice, whereas the other parameters related to the blood vessels and endothelial cells were similar. The deposition of collagen and fibronectin and the expression of collagen 1a1 and 3a1 genes were significantly reduced in α-KO mice. There was a significantly decrease in the number and dividing fibroblasts in the α-KO mice and those of macrophages were similar between the two genotypes. Hepatocyte growth factor ( Hgf ) gene expression was suppressed in Pdgfra -inactivated fibroblasts and connective tissue. The findings implicate the role of PDGFRα-dependent ECM and HGF production in fibroblasts that promotes the remodeling of connective tissue and suggest that PDGFRα may be a relevant target to regulate connective tissue remodeling.
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The Pdgf pathway is crucial to disease pathogenesis.
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- Authors
- Horikawa, S., Ishii, Y., Hamashima, T., Yamamoto, S., Mori, H., Fujimori, T., Shen, J., Inoue, R., Nishizono, H., Itoh, H., Majima, M., Abraham, D., Miyawaki, T., & Sasahara, M.
- Affiliations
- University of Toyama (JP)
- National Institute for Basic Biology (JP)
- Yamaguchi University (JP)
- Kitasato University (JP)
- The Royal Free Hospital (GB)
- Corresponding author
- Yamamoto, Seiji
- ORCID
- Venue
- Scientific Reports
- Published
- 2015-12-07
- Volume
- 5
- Issue
- 1
- Pages
- 17948-17948
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4671150
- OpenAlex
- W2441075516
- Cited by
- 98
- References
- 59
- Citations by year
- 2026: 16 · 2025: 16 · 2024: 2 · 2023: 7 · 2022: 10 · 2021: 14 · 2020: 11 · 2019: 6 · 2018: 5 · 2017: 9 · 2016: 2
- FWCI
- 5.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (23590444, CREST)
- Versus Arthritis (18420)
- Japan Society for the Promotion of Science (26293055, 15K08396, 26460360, 15K15056, 25293093)
- Japan Science and Technology Agency (CREST)
- Core Research for Evolutional Science and Technology
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- PDGFRA, platelet-derived growth factor, connective tissue remodeling, fibroblasts, hepatocyte growth factor, extracellular matrix, collagen deposition, neovascularization, macrophages, knockout mice
- MeSH terms
- Animals, Blood Vessels, Cell Count, Collagen, Connective Tissue, Extracellular Matrix, Fibroblasts, Fibronectins, Fluorescent Antibody Technique, Mice, Inbred C57BL, Skin, Tamoxifen, Hepatocyte Growth Factor, Mice, Knockout, Neovascularization, Physiologic, Implants, Experimental, Receptor, Platelet-Derived Growth Factor alpha
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