A new role of substance P as an injury-inducible messenger for mobilization of CD29+ stromal-like cells
Abstract
Tissue injury may create a specific microenvironment for inducing the systemic participation of stromal-like cells in the repair process. Here we show that substance P is an injury-inducible factor that acts early in the wound healing process to induce CD29(+) stromal-like cell mobilization. Likewise, mobilization of such cells also occurs in uninjured mice, rats and rabbits if substance P is intravenously injected. Upon further characterization these substance P-mobilized CD29(+) cells were found to be similar to stromal cells from a number of connective tissues, including bone marrow (that is, bone marrow stromal cells, or BMSCs). Both substance P injection and transfusion of autologously derived substance P-mobilized CD29(+) cells from uninjured rabbits accelerated wound healing in an alkali burn model. Also, epithelial engraftment of the transfused cells into the injured tissue occurred during the wound healing. Finally, using human BMSCs as a test population, we show that substance P stimulates transmigration, cell proliferation, activation of the extracellular signal-related kinases (Erk) 1 and 2 and nuclear translocation of beta-catenin in vitro. This finding highlights a previously undescribed function of substance P as a systemically acting messenger of injury and a mobilizer of CD29(+) stromal-like cells to participate in wound healing.
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SP acts as an immune modulator and injury messenger in various peripheral tissues.
“Indeed, SP acts as an immune modulator and injury messenger in various peripheral tissues52.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [52]
SP mobilizes mesenchymal stem cells and endothelial progenitor cells in bone marrow and induces them to migrate into injured peripheral tissues where they are involved in tissue regeneration.
“Furthermore, SP mobilizes mesenchymal stem cells52 and endothelial progenitor cells (EPCs)53 in the bone marrow, and induces them to migrate into the injured peripheral tissues where they are involved in tissue regeneration.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [52]
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- Authors
- Hong, H. S., Lee, J., Lee, E., Kwon, Y. S., Lee, E., Ahn, W., Jiang, M. H., Kim, J. C., & Son, Y.
- Affiliations
- Kyung Hee University (KR)
- Chung-Ang University Hospital (KR)
- Corresponding author
- Kim, Jae Chan
- Son, Youngsook
- Venue
- Nature Medicine
- Published
- 2009-03-08
- Volume
- 15
- Issue
- 4
- Pages
- 425-435
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2015214016
- Cited by
- 349
- References
- 46
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 9 · 2023: 21 · 2022: 22 · 2021: 22 · 2020: 26 · 2019: 29 · 2018: 25 · 2017: 34 · 2016: 33 · 2015: 25 · 2014: 32 · 2013: 17 · 2012: 16
- FWCI
- 12.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- substance P, mesenchymal stem cells, wound healing, tissue damage, cell mobilization, alkali burn, ERK signaling, β-catenin nuclear translocation, cell transmigration, cell proliferation
- MeSH terms
- Animals, Bone Marrow Cells, Cell Movement, Eye Injuries, Interleukin-1, Rabbits, Regeneration, RNA, Messenger, Substance P, Tumor Necrosis Factor-alpha, Wound Healing, Stromal Cells, Integrin beta1, Hematopoietic Stem Cell Mobilization, Pluripotent Stem Cells, beta Catenin, Mice, Hypoxia-Inducible Factor 1, alpha Subunit
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