Substance P enhances EPC mobilization for accelerated wound healing
Abstract
Wound healing is essential for the survival and tissue homeostasis of unicellular and multicellular organisms. The current study demonstrated that the neuropeptide substance P (SP) accelerated the wound healing process, particularly in the skin. Subcutaneous treatment of SP accelerated wound closing, increased the population of α‐smooth muscle actin positive myofibroblasts, and increased extracellular matrix deposition at the wound site. Moreover, SP treatment enhances angiogenesis without a local increase in the expression levels of vascular endothelial growth factor and stromal cell‐derived factor‐1. Importantly, SP treatment increased both the population of circulating endothelial progenitor cells in the peripheral blood and in CD31 positive cells in Matrigel plugs. The tube forming potential of endothelial cells was also enhanced by SP treatment. The results suggested that the subcutaneous injection of SP accelerated the wound healing in the skin via better reconstitution of blood vessels, which possibly followed an increase in the systemic mobilization of endothelial progenitor cells and a more effective assembly of endothelial cells into tubes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Subcutaneous administration of SP accelerates the normal acute wound healing response via increased angiogenesis resulting from SP-mediated EPC mobilization.
“Subcutaneous administration of SP accelerates the normal acute wound healing response via increased angiogenesis, resulting from SP-mediated EPC mobilization57.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [57]
Cites
Isolation of Putative Progenitor Endothelial Cells for Angiogenesis
Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G., & Isner, J. M. (1997) · Science · doi:10.1126/science.275.5302.964 · Cited by 8,725 · see citing works
Asahara, T., Masuda, H., Takahashi, T., Kalka, C., Pastore, C., Silver, M., Kearne, M., Magner, M., & Isner, J. M. (1999) · Circulation Research · doi:10.1161/01.res.85.3.221 · Cited by 3,249 · see citing works
Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1
Ceradini, D. J., Kulkarni, A. R., Callaghan, M. J., Tepper, O. M., Bastidas, N., Kleinman, M. E., Capla, J. M., Galiano, R. D., Levine, J. P., & Gurtner, G. C. (2004) · Nature Medicine · doi:10.1038/nm1075 · Cited by 2,600 · see citing works
Takahashi, T., Kalka, C., Masuda, H., Chen, D., Silver, M., Kearney, M., Magner, M., Isner, J. M., & Asahara, T. (1999) · Nature Medicine · doi:10.1038/7434 · Cited by 2,421 · see citing works
Asahara, T., Takahashi, T., Masuda, H., Kalka, C., Chen, D., Iwaguro, H., Inai, Y., Silver, M., & Isner, J. M. (1999) · The EMBO Journal · doi:10.1093/emboj/18.14.3964 · Cited by 1,856 · see citing works
Vascular Endothelial Growth Factor and Angiogenesis
Hoeben, A., Landuyt, B., Highley, M. S., Wildiers, H., Van Oosterom, A. T., & De Bruijn, E. A. (2004) · Pharmacological Reviews · doi:10.1124/pr.56.4.3 · Cited by 1,824 · see citing works
Mesenchymal Stem Cells Enhance Wound Healing Through Differentiation and Angiogenesis
Wu, Y., Chen, L., Scott, P. G., & Tredget, E. E. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0226 · Cited by 1,680 · see citing works
Formation and function of the myofibroblast during tissue repair
Hinz, B. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700613 · Cited by 1,658 · see citing works
Yamaguchi, J.-I., Kusano, K. F., Masuo, O., Kawamoto, A., Silver, M., Murasawa, S., Bosch‐Marcé, M., Masuda, H., Losordo, D. W., Isner, J. M., et al. (2003) · Circulation · doi:10.1161/01.cir.0000055313.77510.22 · Cited by 1,149 · see citing works
Eto, T., & Takahashi, H. (1999) · Nature Medicine · doi:10.1038/8462 · Cited by 914 · see citing works
Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo
Kaushal, S., Amiel, G. E., Guleserian, K. J., Shapira, O. M., Perry, T. E., Sutherland, F. W. H., Aikawa, E. R., Moran, A. M., Schöen, F. J., Atala, A., et al. (2001) · Nature Medicine · doi:10.1038/nm0901-1035 · Cited by 841 · see citing works
Galiano, R. D., Tepper, O. M., Pelo, C. R., Bhatt, K. A., Callaghan, M. J., Bastidas, N., Bunting, S., Steinmetz, H., & Gurtner, G. C. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63754-6 · Cited by 801 · see citing works
Shaw, T. J., & Martin, P. B. (2009) · Journal of Cell Science · doi:10.1242/jcs.031187 · Cited by 771 · see citing works
Altered nociception, analgesia and aggression in mice lacking the receptor for substance P
Felipe, C. D., Herrero, J. F., O’Brien, J., Palmer, J. A., Doyle, C. A., Smith, A. J. H., Laird, J. M. A., Belmonte, C., Cerveró, F., & Hunt, S. P. (1998) · Nature · doi:10.1038/32904 · Cited by 755 · see citing works
Gallagher, K. A., Liu, Z., Xiao, M., Chen, H., Goldstein, L. J., Buerk, D. G., Nedeau, A. E., Thom, S. R., & Velazquez, O. C. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29710 · Cited by 667 · see citing works
The SDF-1–CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis
Petit, I., Jin, D. K., & Rafii, S. (2007) · Trends in Immunology · doi:10.1016/j.it.2007.05.007 · Cited by 605 · see citing works
β-Catenin Defines Head Versus Tail Identity During Planarian Regeneration and Homeostasis
Gurley, K. A., Rink, J. C., & Alvarado, A. S. (2008) · Science · doi:10.1126/science.1150029 · Cited by 469 · see citing works
Hong, H. S., Lee, J., Lee, E., Kwon, Y. S., Lee, E., Ahn, W., Jiang, M. H., Kim, J. C., & Son, Y. (2009) · Nature Medicine · doi:10.1038/nm.1909 · Cited by 349 · see citing works
Wound Repair: Toward Understanding and Integration of Single-Cell and Multicellular Wound Responses
Sonnemann, K. J., & Bement, W. M. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154251 · Cited by 307 · see citing works
Recent advances into the understanding of mesenchymal stem cell trafficking
Fox, J. M., Chamberlain, G., Ashton, B. A., & Middleton, J. (2007) · British Journal of Haematology · doi:10.1111/j.1365-2141.2007.06610.x · Cited by 304 · see citing works
Substance P stimulates neovascularization in vivo and proliferation of cultured endothelial cells
Ziche, M., Morbidelli, L., Pacini, M., Geppetti, P., Alessandri, G., & Maggi, C. A. (1990) · Microvascular Research · doi:10.1016/0026-2862(90)90024-l · Cited by 288 · see citing works
Bhattacharya, V., McSweeney, P. A., Shi, Q., Bruno, B., Ishida, A., Nash, R. A., Storb, R. F., Sauvage, L. R., Hammond, W. P., & Wu, M. H.-D. (2000) · Blood · doi:10.1182/blood.v95.2.581 · Cited by 271 · see citing works
Jujo, K., Hamada, H., Iwakura, A., Thorne, T., Sekiguchi, H., Clarke, T., Ito, A., Misener, S., Tanaka, T. D., Klyachko, E. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914248107 · Cited by 214 · see citing works
Intrathecal substance P and somatostatin in rats: Behaviors indicative of sensation
Seybold, V. S., Hylden, J. L. K., & Wilcox, G. L. (1982) · Peptides · doi:10.1016/0196-9781(82)90141-3 · Cited by 168 · see citing works
Intrathecal substance P and somatostatin in rats: behaviors indicative of sensation
&NA;, &. (1983) · Pain · doi:10.1016/0304-3959(83)90053-2 · Cited by 167 · see citing works
Behavioral evidence that substance P may be a spinal cord sensory neurotransmitter
Piercey, M. F., Dobry, P. J. K., Schroeder, L. A., & Einspahr, F. J. (1981) · Brain Research · doi:10.1016/0006-8993(81)90918-5 · Cited by 148 · see citing works
The cell biology of regeneration
King, R. S., & Newmark, P. A. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201105099 · Cited by 130 · see citing works
Exogenous Administration of Substance P Enhances Wound Healing in a Novel Skin-Injury Model
Delgado, Á. V., McManus, A. T., & Chambers, J. P. (2005) · Experimental Biology and Medicine · doi:10.1177/153537020523000407 · Cited by 116 · see citing works
Shepherd, R. M., Capoccia, B. J., Devine, S. M., DiPersio, J. F., Trinkaus, K. M., Ingram, D. A., & Link, D. C. (2006) · Blood · doi:10.1182/blood-2006-06-030577 · Cited by 116 · see citing works
CXCR4 Antagonist AMD3100 Accelerates Impaired Wound Healing in Diabetic Mice
Nishimura, Y., Ii, M., Qin, G., Hamada, H., Asai, J., Takenaka, H., Sekiguchi, H., Renault, M., Jujo, K., Katoh, N., et al. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.356 · Cited by 107 · see citing works
Amadesi, S., Reni, C., Katare, R., Meloni, M., Oikawa, A., Beltrami, A. P., Avolio, E., Cesselli, D., Fortunato, O., Spinetti, G., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.089763 · Cited by 100 · see citing works
Burssens, P., Steyaert, A., Forsyth, R. G., van Ovost, E., Paepe, Y. D., & Verdonk, R. C. (2005) · Foot & Ankle International · doi:10.1177/107110070502601008 · Cited by 98 · see citing works
Drosophila as a model of wound healing and tissue regeneration in vertebrates
Belacortu, Y., & Paricio, N. (2011) · Developmental Dynamics · doi:10.1002/dvdy.22753 · Cited by 98 · see citing works
Turabelidze, A., Guo, S., & DiPietro, L. A. (2010) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2010.00611.x · Cited by 86 · see citing works
Bauer, S. M., Goldstein, L. J., Bauer, R. J., Chen, H., Putt, M. E., & Velazquez, O. C. (2006) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2005.08.038 · Cited by 85 · see citing works
Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats
Kant, V., Kumar, D., Kumar, D., Prasad, R., Gopal, A., Pathak, N. N., Kumar, P., & Tandan, S. K. (2015) · Cytokine · doi:10.1016/j.cyto.2014.12.015 · Cited by 79 · see citing works
Aicher, A., Kollet, Ó., Heeschen, C., Liebner, S., Urbich, C., Ihling, C. H., Orlandi, A., Lapidot, T., Zeiher, A. M., & Dimmeler, S. (2008) · Circulation Research · doi:10.1161/circresaha.107.172718 · Cited by 73 · see citing works
Teodoro, F. C., Júnior, M. F. T., Zampronio, A. R., Martini, A. C., Rae, G. A., & Chichorro, J. G. (2012) · Neuropeptides · doi:10.1016/j.npep.2012.10.005 · Cited by 66 · see citing works
Topically applied substance P enhanced healing of open excision wound in rats
Kant, V., Gopal, A., Kumar, D., Bag, S., Kurade, N. P., Kumar, A., Tandan, S. K., & Kumar, D. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.04.042 · Cited by 60 · see citing works
Yin, Y., Huang, L. J., Zhao, X., Fang, Y., Yu, S., Zhao, J., & Cui, B. (2007) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3180587e4d · Cited by 52 · see citing works
Jiang, M., Lim, J. E., Chi, G. F., Ahn, W., Zhang, M., Chung, E., & Son, Y. (2013) · Neuroreport · doi:10.1097/wnr.0b013e3283650e3d · Cited by 43 · see citing works
Dubon, M. J., & Park, K. (2015) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2015.2291 · Cited by 25 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Wound healing: cellular mechanisms and pathological outcomes
Wilkinson, H. N., & Hardman, M. J. (2020) · Open Biology · doi:10.1098/rsob.200223 · Cited by 1,886 · see citing works
Poloxamer: A versatile tri-block copolymer for biomedical applications
Zarrintaj, P., Ramsey, J. D., Samadi, A., Atoufi, Z., Yazdi, M. K., Saeb, M. R., Amirabad, L. M., Zangene, E., Farokhi, M., Formela, K., et al. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.04.028 · Cited by 411 · see citing works
Toll-Like Receptor Function in Acute Wounds
Chen, L., & DiPietro, L. A. (2017) · Advances in Wound Care · doi:10.1089/wound.2017.0734 · Cited by 118 · see citing works
Yan, D., Liu, X., & Guo, S.-W. (2019) · Scientific Reports · doi:10.1038/s41598-019-39170-w · Cited by 82 · see citing works
Zhou, Z., Sui, X., Cao, Z., Li, X., Qing, L., & Tang, J. (2023) · Peptides · doi:10.1016/j.peptides.2023.171045 · Cited by 50 · see citing works
Substance P participates in periodontitis by upregulating HIF-1α and RANKL/OPG ratio
Yan, K., Lin, Q., Tang, K., Liu, S., Du, Y., Yu, X., & Li, S. (2020) · BMC Oral Health · doi:10.1186/s12903-020-1017-9 · Cited by 48 · see citing works
Um, J., Yu, J., & Park, K. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6344 · Cited by 40 · see citing works
Self-citationMehta, D., & Granstein, R. D. (2019) · Dermatology · doi:10.1159/000496538 · Cited by 40 · see citing works
The Regenerative Potential of Substance P
Redkiewicz, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020750 · Cited by 38 · see citing works
Neuropeptides, Inflammation, Biofilms, and diabetic Foot Ulcers
Yang, S., Hu, L., Han, R., & Yang, Y. (2021) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-1493-0458 · Cited by 37 · see citing works
Shafiq, M., Wang, L., Zhi, D., Zhang, Q., Wang, K., Wang, L., Kim, D., Kong, D., & Kim, S. H. (2019) · Journal of Biomedical Materials Research Part B: Applied Biomaterials · doi:10.1002/jbm.b.34260 · Cited by 30 · see citing works
Neuropeptide Substance P Enhances Skin Wound Healing In Vitro and In Vivo under Hypoxia
Kumar, S., Tan, Y., & Francois Berthiaume, B. (2021) · Biomedicines · doi:10.3390/biomedicines9020222 · Cited by 26 · see citing works
Xing, L., Chen, B., Qin, Y., Li, X., Zhou, S., Yuan, K., Zhao, R., & Qin, D. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1494865 · Cited by 27 · see citing works
Wu, J., Liu, S., Wang, Z., Ma, S., Meng, H., & Hu, J. (2018) · Proteome Science · doi:10.1186/s12953-018-0146-4 · Cited by 25 · see citing works
Park, S. J., Cho, W., Kim, M. S., Gu, B. K., Kang, C. M., Khang, G., & Kim, C. (2017) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2445 · Cited by 24 · see citing works
Yu, J., Nam, D., & Park, K. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.11.172 · Cited by 24 · see citing works
Self-citationNeuromodulation of bone: Role of different peptides and their interactions (Review)
Wang, X., Xu, J., & Kang, Q. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.11670 · Cited by 23 · see citing works
Leal, V. M. J., Ribeiro, C., Oliveiros, B., António, N., & Silva, S. (2018) · Stem Cell Reviews and Reports · doi:10.1007/s12015-018-9857-2 · Cited by 24 · see citing works
Neuropeptide substance P: A promising regulator of wound healing in diabetic foot ulcers
Chen, J., Ye, P., Gu, R., Zhu, H., He, W., Mu, X., Wu, X., Pang, H., Han, F. Y., & Nie, X. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115736 · Cited by 23 · see citing works
Liu, S., Chen, T., Wang, R., Huang, H., Fu, S., Zhao, Y., Wang, S., & Wan, L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.908043 · Cited by 21 · see citing works
Yu, J., Choi, S., Um, J., & Park, K. (2017) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-016-0019-9 · Cited by 18 · see citing works
Self-citationEicosanoids: Emerging contributors in stem cell-mediated wound healing
Berry, E. L., Liu, Y., Chen, L., & Guo, A. M. (2016) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2016.11.001 · Cited by 17 · see citing works
The neuropeptide substance P/neurokinin‐1 receptor system and diabetes: From mechanism to therapy
Kokabi, F., Ebrahimi, S., Mirzavi, F., Nooghabi, N. G., Hashemi, S. F., & Hashemy, S. I. (2023) · BioFactors · doi:10.1002/biof.1935 · Cited by 14 · see citing works
Shafiq, M., & Kim, S. H. (2016) · Macromolecular Research · doi:10.1007/s13233-016-4134-1 · Cited by 13 · see citing works
Serini, S., & Calviello, G. (2021) · Foods · doi:10.3390/foods10102306 · Cited by 14 · see citing works
Development of Neuropeptide Hemokinin-1 Analogues with Antimicrobial and Wound-Healing Activity
Yao, Y., Zhang, W., Li, S., Xie, H., Zhang, Z., Jia, B., Huang, S., Li, W., Ma, L., Gao, Y., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c02021 · Cited by 13 · see citing works
The recent research progress of polyphenol‐derived biomaterials in wound repair
Zhao, S., Han, L., Yan, L., & Lu, X. (2023) · Biosurface and Biotribology · doi:10.1049/bsb2.12074 · Cited by 4 · see citing works
Mahmoudi, N., Lesieur, R., Rey, S., dos Santos, B. P., Catros, S., Garbay, B., Amédée, J., & Roque, M. (2026) · Regenerative Biomaterials · doi:10.1093/rb/rbag036 · Cited by 1 · see citing works
Substance P-neurokinin 1 receptor pathway in musculoskeletal disorders
Hilliard, B. A., & Barbe, M. F. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-22194-1.00022-7
Endothelial system dysregulation underlies keloid development and therapeutic targeting
Yu, Y., Zhu, J., Ma, L., Zhang, X., & Yan, H. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1919403
Wu, J., Zhao, M., Wu, H., Duan, X., Tian, D., Xu, S., Shi, T., Lan, J., Wang, Z., Wang, J., et al. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1924507
- Authors
- Um, J., Jung, N., Chin, S., Cho, Y., Choi, S., & Park, K.
- Affiliations
- Kyung Hee University (KR)
- Corresponding author
- Park, Ki‐Sook
- Venue
- Wound Repair and Regeneration
- Publisher
- Wiley
- Published
- 2016-02-18
- Volume
- 24
- Issue
- 2
- Pages
- 402-410
- ISSN
- 1067-1927 (ISSN-L)
- 1524-475X
- OpenAlex
- W2230911448
- Cited by
- 32
- References
- 42
- Citations by year
- 2026: 3 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 2
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Wound Repair and Regeneration (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2012R1A1A2042265, NRF-2015R1D1A1A09057839)
- Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI13C1479)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- substance P, wound healing, endothelial progenitor cells, EPC mobilization, angiogenesis, myofibroblasts, extracellular matrix deposition, skin wound closure, neuropeptides, endothelial tube formation, vascular endothelial growth factor, CXCL12
- MeSH terms
- Animals, Cell Movement, Collagen, Disease Models, Animal, Drug Combinations, Extracellular Matrix, Immunohistochemistry, Laminin, Male, Mice, Inbred C57BL, Proteoglycans, Substance P, Wound Healing, Wounds and Injuries, Neurotransmitter Agents, Neovascularization, Physiologic, Vascular Endothelial Growth Factor A, Mice, Chemokine CXCL12, Endothelial Progenitor Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
