Direct contact of fibroblasts with neuronal processes promotes differentiation to myofibroblasts and induces contraction of collagen matrix in vitro
Abstract
Wound healing is often delayed in the patients whose sensory and autonomic innervation is impaired. We hypothesized that existence of neurites in the skin may promote wound healing by inducing differentiation of fibroblasts into myofibroblasts with consequent wound contraction. In the current study, we examined the effect of neurons on differentiation of fibroblasts and contraction of collagen matrix in vitro using a new co‐culture model. Neuronal cell line, PC12 cells, of which the neurite outgrowth can be controlled by adding nerve growth factor, was used. Rat dermal fibroblasts were co‐cultured with PC12 cells extending neurites or with PC12 cells lacking neurites. Then, differentiation of fibroblasts into myofibroblasts and contraction of the collagen matrix was evaluated. Finally, we examined whether direct or indirect contact with neurites of PC12 cells promoted the differentiation of fibroblasts. Our results showed that fibroblasts co‐cultured with PC12 extending neurites differentiated into myofibroblasts more effectively and contracted the collagen matrix stronger than those with PC12 lacking neurites. Direct contact of fibroblasts with neurites promoted more differentiation than indirect contact. In conclusion, direct contact of fibroblasts with neuronal processes is important for differentiation into myofibroblasts and induction of collagen gel contraction, leading to promotion of wound healing.
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Direct contact of fibroblasts with neuronal processes promotes differentiation to myofibroblasts and their contractility.
“Direct contact of fibroblasts with neuronal processes promotes differentiation to myofibroblasts and their contractility82.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [82]
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The myofibroblast, a key cell in normal and pathological tissue repair
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- Authors
- Fujiwara, T., Kubo, T., Kanazawa, S., Shingaki, K., Taniguchi, M., Matsuzaki, S., Gurtner, G. C., Tohyama, M., & Hosokawa, K.
- Affiliations
- Department of Plastic Surgery Osaka University Graduate School of Medicine Osaka Japan
- The University of Osaka (JP)
- Stanford Medicine (US)
- Corresponding author
- Kubo, Tateki
- Venue
- Wound Repair and Regeneration
- Publisher
- Wiley
- Published
- 2013-06-11
- Volume
- 21
- Issue
- 4
- Pages
- 588-594
- ISSN
- 1067-1927 (ISSN-L)
- 1524-475X
- OpenAlex
- W1951736946
- Cited by
- 31
- References
- 37
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 5 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 3
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Wound Repair and Regeneration (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Planarian Biology and Electrostimulation
- Keywords
- myofibroblast differentiation, fibroblasts, neurites, collagen matrix contraction, wound healing, PC12 cells, nerve growth factor, dermal fibroblasts, sensory innervation, direct cell contact
- MeSH terms
- Animals, Cell Communication, Cell Differentiation, Cells, Cultured, Collagen, Extracellular Matrix, Fibroblasts, Neurons, Wound Healing, Neurites, PC12 Cells, Coculture Techniques, Dermis, Nerve Growth Factor, Rats, Myofibroblasts
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