17β‐Estradiol administration promotes delayed cutaneous wound healing in 40‐week ovariectomised female mice
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This study investigated the effect of 17β‐estradiol on wound healing in 40‐week ovariectomised female mice. Thirty‐six‐week‐old female mice were divided into three groups: medication with 17β‐estradiol after ovariectomy (OVX + 17β‐estradiol), ovariectomy (OVX) and sham (SHAM). The mice received two full‐thickness wounds, and the OVX + 17β‐estradiol group was administered 17β‐estradiol at 0·01 g/day until healing. In the OVX + 17β‐estradiol group, the ratio of wound area was significantly smaller than those of the OVX and SHAM groups on days 1–3, 5, 6, 8–12 and 9–12, respectively, the numbers of neutrophils and macrophages were significantly smaller than those on days 3 and 7, the ratio of re‐epithelialisation was significantly higher than those on days 3 and 11, the ratio of myofibroblasts was significantly higher than those on day 11 and smaller on day 14, and the ratio of collagen fibres was significantly larger than that of the OVX group on days 7–14. We found that 17β‐estradiol administration promotes cutaneous wound healing in 40‐week female mice by reducing wound area, shortening inflammatory response, and promoting re‐epithelialisation, collagen deposition and wound contraction. Our results suggest that cutaneous wound healing that is delayed because of ageing is promoted by exogenous and continuous 17β‐estradiol administration.
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Estrogen is important to wound healing, and its deficiency delays or impairs wound healing.
“Numerous studies have shown that estrogen is important to wound healing, and its deficiency delays or impairs wound healing29–33.”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [33]
Cites
Shaw, T. J., & Martin, P. B. (2009) · Journal of Cell Science · doi:10.1242/jcs.031187 · Cited by 771 · see citing works
Estrogen accelerates cutaneous wound healing associated with an increase in TGF-β1 levels
Ashcroft, G. S., Dodsworth, J., Boxtel, E. V., Tarnuzzer, R. W., Horan, M. A., Schultz, G. S., & Ferguson, M. W. J. (1997) · Nature Medicine · doi:10.1038/nm1197-1209 · Cited by 573 · see citing works
Ashcroft, G. S., Greenwell-Wild, T., Horan, M. A., Wahl, S. M., & Ferguson, M. W. J. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65217-0 · Cited by 420 · see citing works
Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor
Ashcroft, G. S., Mills, S. J., Lei, K., Gibbons, L., Jeong, M.-J., Taniguchi, M., Burow, M., Horan, M. A., Wahl, S. M., & Nakayama, T. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16288 · Cited by 335 · see citing works
Age-Related Aspects of Cutaneous Wound Healing: A Mini-Review
Sgonc, R., & Gruber, J. (2013) · Gerontology · doi:10.1159/000342344 · Cited by 288 · see citing works
Nelson, J. F., Felicio, L. S., Osterburg, H. H., & Finch, C. E. (1981) · Biology of Reproduction · doi:10.1095/biolreprod24.4.784 · Cited by 223 · see citing works
Moran, A. L., Nelson, S. A., Landisch, R. M., Warren, G. L., & Lowe, D. A. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01305.2006 · Cited by 208 · see citing works
(1998) · PubMed · Cited by 203 · see citing works
Ashcroft, G. S., Horan, M. A., Herrick, S. E., Tarnuzzer, R. W., Schultz, G. S., & Ferguson, M. W. J. (1997) · Cell and Tissue Research · doi:10.1007/s004410050963 · Cited by 188 · see citing works
Campbell, L., Emmerson, E., Davies, F., Gilliver, S. C., Krust, A., Chambon, P., Ashcroft, G. S., & Hardman, M. J. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100500 · Cited by 175 · see citing works
Sadoun, E., & Reed, M. J. (2003) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540305100902 · Cited by 158 · see citing works
Estrogen, not intrinsic aging, is the major regulator of delayed human wound healing in the elderly
Hardman, M. J., & Ashcroft, G. S. (2008) · Genome Biology · doi:10.1186/gb-2008-9-5-r80 · Cited by 157 · see citing works
Herrick, S. E., Ashcroft, G. S., Ireland, G. W., Horan, M. A., McCollum, C. N., & Ferguson, M. W. J. (1997) · PubMed · Cited by 146 · see citing works
Son, E. D., Lee, J., Lee, S., Kim, M. S., Lee, B. G., Chang, I. S., & Chung, J. H. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23736.x · Cited by 136 · see citing works
Hardman, M. J., Emmerson, E., Campbell, L., & Ashcroft, G. S. (2008) · Endocrinology · doi:10.1210/en.2007-1042 · Cited by 117 · see citing works
Papaconstantinou, A. D. (2000) · Toxicological Sciences · doi:10.1093/toxsci/56.2.332 · Cited by 113 · see citing works
Ashcroft, G. S., Horan, M. A., & Ferguson, M. W. J. (1997) · Journal of Anatomy · doi:10.1046/j.1469-7580.1997.19030351.x · Cited by 111 · see citing works
Effect of estrogen and progesterone on macrophage activation during wound healing
Routley, C., & Ashcroft, G. S. (2009) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2008.00440.x · Cited by 103 · see citing works
The phytoestrogen genistein promotes wound healing by multiple independent mechanisms
Emmerson, E., Campbell, L., Ashcroft, G. S., & Hardman, M. J. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.02.026 · Cited by 81 · see citing works
The Sex Steroid Precursor DHEA Accelerates Cutaneous Wound Healing Via the Estrogen Receptors
Mills, S. J., Ashworth, J., Gilliver, S. C., Hardman, M. J., & Ashcroft, G. S. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23926.x · Cited by 74 · see citing works
Emmerson, E., Campbell, L., Ashcroft, G. S., & Hardman, M. J. (2009) · Endocrinology · doi:10.1210/en.2008-1569 · Cited by 51 · see citing works
Novel Locally Active Estrogens Accelerate Cutaneous Wound Healing. A Preliminary Study
Brufani, M., Ceccacci, F., Filocamo, L., Garofalo, B., Joudioux, R., Bella, A. L., Leonelli, F., Migneco, L. M., Bettolo, R. M., Farina, P. M., et al. (2009) · Molecular Pharmaceutics · doi:10.1021/mp800206b · Cited by 18 · see citing works
Flagged first, then by citations
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Göb, E., Reymann, S., Langhauser, F., Schuhmann, M. K., Kraft, P., Thielmann, I., Göbel, K., Brede, M., Homola, G. A., Solymosi, L., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24380 · Cited by 103 · see citing works
Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair
Crompton, R. A., Williams, H., Ansell, D. M., Campbell, L., Holden, K. A., Cruickshank, S. M., & Hardman, M. J. (2016) · Laboratory Investigation · doi:10.1038/labinvest.2015.160 · Cited by 60 · see citing works
Qi, Q., Liu, X., Zhang, Q., & Guo, S.-W. (2020) · Scientific Reports · doi:10.1038/s41598-020-57997-6 · Cited by 44 · see citing works
Mukai, K., Urai, T., Asano, K., Nakajima, Y., & Nakatani, T. (2016) · PLoS ONE · doi:10.1371/journal.pone.0163560 · Cited by 37 · see citing works
Self-citationLoffredo, L. F., Coden, M. E., & Berdnikovs, S. (2020) · Nutrients · doi:10.3390/nu12020343 · Cited by 35 · see citing works
The effects of oestrogen on vaginal wound healing: A systematic review and meta‐analysis
Vodegel, E. V., Kastelein, A. W., Jansen, C. H. J. R., Limpens, J., Zwolsman, S. E., Roovers, J., Hooijmans, C. R., & Güler, Z. (2021) · Neurourology and Urodynamics · doi:10.1002/nau.24819 · Cited by 33 · see citing works
Various types of adenomyosis and endometriosis: in search of optimal management
Guo, S. (2023) · Fertility and Sterility · doi:10.1016/j.fertnstert.2023.03.021 · Cited by 24 · see citing works
Mukai, K., Komatsu, E., Nakajima, Y., Urai, T., Nasruddin, N., Sugama, J., & Nakatani, T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115564 · Cited by 24 · see citing works
Self-citationMukai, K., Horike, S., Meguro‐Horike, M., Nakajima, Y., Iswara, A., & Nakatani, T. (2022) · PLoS ONE · doi:10.1371/journal.pone.0264572 · Cited by 21 · see citing works
Self-citationMukai, K., Nakajima, Y., Asano, K., & Nakatani, T. (2019) · PLoS ONE · doi:10.1371/journal.pone.0225880 · Cited by 20 · see citing works
Self-citationThe contradictory role of androgens in cutaneous and major burn wound healing
Shi, H., Cheer, K., Simanainen, U., Lesmana, B., Ma, D., Hew, J. J., Parungao, R., Li, Z., Cooper, M. S., Handelsman, D. J., et al. (2020) · Burns & Trauma · doi:10.1093/burnst/tkaa046 · Cited by 20 · see citing works
Nasruddin, N., Putri, I. K., Kamal, S., Rahayu, H. S. E., Lutfiyati, H., Pribadi, P., Kusuma, T. M., Muhlisin, Z., Nur, M., Nurani, L. H., et al. (2017) · Clinical Plasma Medicine · doi:10.1016/j.cpme.2017.03.001 · Cited by 20 · see citing works
Self-citationWahyuningtyas, E. S., Iswara, A., Sari, Y., Kamal, S., Santosa, B., Ishijima, T., Nakatani, T., Putri, I. K., & Nasruddin, N. (2018) · Clinical Plasma Medicine · doi:10.1016/j.cpme.2018.08.001 · Cited by 18 · see citing works
Self-citationThe Role of Platelets in the Pathogenesis and Pathophysiology of Adenomyosis
Guo, S. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12030842 · Cited by 17 · see citing works
Iswara, A., Tanaka, K., Ishijima, T., Nakajima, Y., Mukai, K., Tanaka, Y., Nakano, Y., Sugama, J., Oe, M., Okuwa, M., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0275602 · Cited by 14 · see citing works
Self-citationRahayu, H. S. E., Nasruddin, N., Nurani, L. H., Darmawati, S., Rohmani, A., Lutfiyati, H., Wahyuningtyas, E. S., Sikumbang, I. M., Muhlisin, Z., Sukeksi, A., et al. (2019) · Clinical Plasma Medicine · doi:10.1016/j.cpme.2019.100090 · Cited by 12 · see citing works
Self-citationCogan, N. G., Mellers, A. P., Patel, B. N., Powell, B. D., Aggarwal, M., Harper, K. M., & Blaber, M. (2018) · Wound Repair and Regeneration · doi:10.1111/wrr.12634 · Cited by 8 · see citing works
Hagerott, B. N., Blumstein, A. J., McGarry, L. E., Cohen, H. M., Tenorio, C. A., Powell, B. D., Nagy, T., & Blaber, M. (2020) · Journal of Proteins and Proteomics · doi:10.1007/s42485-020-00040-z · Cited by 7 · see citing works
Shao, Q., Wang, Z., Li, Y.-F., Tang, X., Li, Z., Xia, H., Wu, Q., Chang, R., Wu, C., Meng, T., et al. (2025) · Cells · doi:10.3390/cells14100727 · Cited by 4 · see citing works
Mellers, A. P., Tenorio, C. A., Lacatusu, D. A., Powell, B. D., Patel, B. N., Harper, K. M., & Blaber, M. (2018) · Advances in Wound Care · doi:10.1089/wound.2018.0801 · Cited by 3 · see citing works
Mukai, K., Zhu, W., Nakajima, Y., Kobayashi, M., & Nakatani, T. (2017) · Skin Research and Technology · doi:10.1111/srt.12374 · Cited by 3 · see citing works
Self-citationSharma, S., Horton, I., Josyula, A., & Sadtler, K. (2026) · Biomaterials Science · doi:10.1039/d5bm01334h · Cited by 1 · see citing works
Pathogenesis of Endometriosis: Role of Platelets in Endometriosis
Guo, S. (2022) · Springer eBooks · doi:10.1007/978-3-030-97236-3_4 · Cited by 1 · see citing works
Motoi, A., Tajima, K., Motoi, R., Motoi, M., Amano, H., Yamanaka, D., Ishibashi, K., Ohno, N., & Adachi, Y. (2024) · International journal of medicinal mushrooms · doi:10.1615/intjmedmushrooms.2024054886
Sari, K., Dayani, L., Poorirani, S., Heydari, P., Ghaffari‐Tabrizi‐Wizsy, N., & Mostafavi, S. A. (2025) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2025.126386
Iswara, A., Kanae, M., Nakajima, Y., Koizumi, D., Iohara, K., & Nakatani, T. (2026) · Health · doi:10.4236/health.2026.185028
Self-citationde Souza, A., Sarandy, M. M., Novaes, R. D., Valacchi, G., & Gonçalves, R. V. (2026) · Journal of King Saud University - Science · doi:10.25259/jksus_1101_2025
- Authors
- Mukai, K., Nakajima, Y., Urai, T., Komatsu, E., Nasruddin, Sugama, J., & Nakatani, T.
- Affiliations
- Kanazawa University (JP)
- Department of Clinical Nursing, Graduate Course of Nursing Science, Division of Health Sciences, Graduate School of Medical, Pharmaceutical and Health Sciences Kanazawa University Kanazawa Japan
- Corresponding author
- Nakatani, Toshio
- Venue
- International Wound Journal
- Publisher
- Wiley
- Published
- 2014-08-06
- Volume
- 13
- Issue
- 5
- Pages
- 636-644
- ISSN
- 1742-4801 (ISSN-L)
- 1742-481X
- PMC
- PMC7949953
- OpenAlex
- W1932164140
- Cited by
- 27
- References
- 23
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 1
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- International Wound Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- JSPS KAKENHI (22592363, 25293430)
- Kanazawa University
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Keywords
- estradiol, skin wound healing, delayed wound healing, ovariectomy, aging, re-epithelialization, collagen deposition, myofibroblasts, wound contraction, inflammation, neutrophils, macrophages, female mice
- MeSH terms
- Administration, Cutaneous, Animals, Estradiol, Female, Ovariectomy, Skin, Wound Healing, Mice
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