The DOI matches its Crossref record; 33 of the 34 references it cites were found in a registry or an index.
Dexamethasone Induction of Keloid Regression through Effective Suppression of VEGF Expression and Keloid Fibroblast Proliferation
Open accessAbstract
The biological mechanism underlying steroid therapy for treating keloids remains unclear. Analytical results demonstrated that topical intra-lesional steroid injections suppress vascular endothelial growth factor (VEGF) expression in keloid tissue and induce its regression in vivo. This study investigated whether glucocorticoid (dexamethasone) downregulates VEGF expression and hinders keloid fibroblast (KF) proliferation in keloid regression. Primary KF cultures were treated with various concentrations of dexamethasone, glucocorticoid receptor (GR) antagonist (mifeprostone, RU-486), VEGF-A antibody, VEGF receptor-2 (VEGF-R2) antagonist (SU-5416), and VEGF protein. Analytical results demonstrated that dexamethasone retarded KFs proliferation. However, suppression of fibroblast proliferation by dexamethasone pre-treatment was reduced by adding exogenous VEGF protein. Dexamethasone suppressed endogenous VEGF mRNA induction, protein expressed by KFs, and angiogenesis activity detected by a tube-forming assay of human umbilical vein endothelial cells co-cultured fibroblasts. These effects were reversed by pre-treatment with RU-486, and not by pre-treatment with SU-5416. Thus, dexamethasone induces keloid regression via interaction with the GR and suppresses endogenous VEGF expression and fibroblast proliferation. However, exogenous VEGF promotes fibroblast proliferation through the GR-independent pathway. Modulation of VEGF production may comprise a valuable treatment modality for keloids.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“glucocorticoids including DX have been shown to decrease the in vivo activity of VEGF.207–209”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [209]
Citations
Cites
Angiogenesis in cancer and other diseases
Carmeliet, P., & Jain, R. K. (2000) · Nature · doi:10.1038/35025220 · Cited by 9,070
Molecular and Biological Properties of the Vascular Endothelial Growth Factor Family of Proteins
Ferrara, N., Houck, K. A., Jakeman, L. B., & LEUNG, D. W. (1992) · Endocrine Reviews · doi:10.1210/edrv-13-1-18 · Cited by 1,655
Growth factors and wound healing: Biochemical properties of growth factors and their receptors
Bennett, N. T., & Schultz, G. S. (1993) · The American Journal of Surgery · doi:10.1016/s0002-9610(05)80797-4 · Cited by 658
Vascular Endothelial Growth Factor, a Potent and Selective Angiogenic Agent
Thomas, K. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.2.603 · Cited by 553
Keloids and Hypertrophic Scars
Rockwell, W. B., Cohen, I. K., & Ehrlich, H. P. (1989) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-198911000-00021 · Cited by 476
Yamakawa, M., Liu, L. X., Date, T., Belanger, A. J., Vincent, K. A., Akita, G. Y., Kuriyama, T., Cheng, S. H., Gregory, R. J., & Jiang, C. (2003) · Circulation Research · doi:10.1161/01.res.0000093984.48643.d7 · Cited by 327
The Effect of TGF-β on Keloid Fibroblast Proliferation and Collagen Synthesis
Bettinger, D. A., Yager, D. R., Diegelmann, R. F., & Cohen, K. I. (1996) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-199610000-00012 · Cited by 294
Keloidal scars: A review with a critical look at therapeutic options
Shaffer, J. J., Taylor, S. C., & Cook-Bolden, F. E. (2002) · Journal of the American Academy of Dermatology · doi:10.1067/mjd.2002.120788 · Cited by 204
Growth kinetics and collagen synthesis of normal skin, normal scar and keloid fibroblasts in vitro
Diegelmann, R. F., Cohen, I. K., & McCoy, B. J. (1979) · Journal of Cellular Physiology · doi:10.1002/jcp.1040980210 · Cited by 202
Intralesional 5-Fluorouracil as a Treatment Modality of Keloids
Nanda, S., & Reddy, B. S. N. (2004) · Dermatologic Surgery · doi:10.1111/j.1524-4725.2004.29382.x · Cited by 173
Downregulation of Apoptosis-Related Genes in Keloid Tissues
Sayah, D. N., Soo, C. B., Shaw, W. W.-L., Watson, J., Messadi, D. V., Longaker, M. T., Zhang, X., & Ting, K. (1999) · Journal of Surgical Research · doi:10.1006/jsre.1999.5761 · Cited by 145
Kiil, J. (1977) · Scandinavian Journal of Plastic and Reconstructive Surgery · doi:10.3109/02844317709025514 · Cited by 139
Keloids and hypertrophic scars
Murray, J. C. S., Pollack, S. V., & Pinnell, S. R. (1984) · Clinics in Dermatology · doi:10.1016/0738-081x(84)90035-x · Cited by 135
Keloids and hypertrophic scars
Murray, J. C. S. (1994) · Clinics in Dermatology · doi:10.1016/0738-081x(94)90254-2 · Cited by 132
Apoptosis, necrosis, and proliferation: possible implications in the etiology of keloids.
Appleton, I. M., Brown, N. J., & Willoughby, D. A. (1996) · PubMed · Cited by 121
Keloids demonstrate high-level epidermal expression of vascular endothelial growth factor
Gira, A. K., Brown, L. F., Washington, C. V., Cohen, C., & Arbiser, J. L. (2004) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2003.11.061 · Cited by 109
Altered cytokine production in black patients with keloids
McCauley, R. L., Chopra, V., Li, Y., Herndon, D. N., & Robson, M. C. (1992) · Journal of Clinical Immunology · doi:10.1007/bf00918154 · Cited by 109
Elevated Interleukin-6 Expression in Keloid Fibroblasts
Xue, H., McCauley, R. L., & Zhang, W. (2000) · Journal of Surgical Research · doi:10.1006/jsre.1999.5805 · Cited by 107
Wu, Y., Zhang, Q., Ann, D. K., Akhondzadeh, A., Duong, H. S., Messadi, D. V., & Le, A. D. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00200.2003 · Cited by 101
Kuo, Y., Jeng, S., Wang, F., Chen, T., Huang, H., Chang, P., & Yang, K. D. (2004) · Lasers in Surgery and Medicine · doi:10.1002/lsm.10206 · Cited by 93
Self-citationHistomorphologic Changes in Keloids Treated with Kenacort
Boyadjiev, C., Popchristova, E., & Mazgalova, J. (1995) · doi:10.1097/00005373-199502000-00030 · Cited by 84
Kuo, Y., Wu, W.-S., Jeng, S., Huang, H.-C., Yang, K. D., Sacks, J. M., & Wang, F. (2005) · Lasers in Surgery and Medicine · doi:10.1002/lsm.20129 · Cited by 82
Self-citationBiological effects of silicone gel sheeting
Borgognoni, L. (2002) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2002.00205.x · Cited by 78
Elevated Vascular Endothelial Growth Factor in Keloids: Relevance to Tissue Fibrosis
Le, A. D., Zhang, Q., Wu, Y., Messadi, D. V., Akhondzadeh, A., Nguyen, A. L., Aghaloo, T. L., Kelly, A., & Bertolami, C. N. (2004) · Cells Tissues Organs · doi:10.1159/000075030 · Cited by 76
Triamcinolone Stimulates bFGF Production and Inhibits TGF-β1 Production by Human Dermal Fibroblasts
Carroll, L. A., Hanasono, M. M., Mikulec, A. A., Kita, M., & KOCH, R. J. (2002) · Dermatologic Surgery · doi:10.1046/j.1524-4725.2002.02012.x · Cited by 75
Hypoxia Upregulates VEGF Production in Keloid Fibroblasts
Steinbrech, D. S., Mehrara, B. J., Chau, D., Rowe, N. M., Chin, G. S., Lee, T., Saadeh, P. B., Gittes, G. K., & Longaker, M. T. (1999) · Annals of Plastic Surgery · doi:10.1097/00000637-199905000-00009 · Cited by 72
Slavin, J. P., Unemori, E., Hunt, T. K., & Amento, E. P. (1994) · Growth Factors · doi:10.3109/08977199409046918 · Cited by 61
Current developments and uses of cryosurgery in the treatment of keloids and hypertrophic scars
Zouboulis, C. C., ZOURIDAKI, E., Rosenberger, A. D., & DALKOWSKI, A. (2002) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2002.02111.x · Cited by 48
The Surgical Treatment of Keloids
Pollack, S. V., & GOSLEN, J. B. (1982) · The Journal of Dermatologic Surgery and Oncology · doi:10.1111/j.1524-4725.1982.tb01092.x · Cited by 46
Glucocorticoid receptors in human fibroblasts derived from normal dermis and keloid tissue.
Gadson, P. F., Russell, J. D., & Russell, S. B. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)90853-7 · Cited by 36
Apoptosis, necrosis, and proliferation: possible implications in the etiology of keloids.
Brown, N., Willoughby, D. A., & Appleton, I. M. (1997) · American Journal of Ophthalmology · doi:10.1016/s0002-9394(14)71108-0 · Cited by 35
Treatment of Earlobe Keloids Using the Cobalt 60 Teletherapy Unit
Malaker, K., Zaidi, M., & Franka, M. R. (2004) · Annals of Plastic Surgery · doi:10.1097/01.sap.0000095408.74866.f1 · Cited by 31
A technique to avoid atrophy in combined intralesional excision and steroid injection for keloids
Patel, I. A., & Hall, P. N. (2000) · British Journal of Plastic Surgery · doi:10.1054/bjps.1999.3306 · Cited by 3
Cited by
Sorted by citations
Vascular Endothelial Growth Factor and Angiogenesis in the Regulation of Cutaneous Wound Repair
Johnson, K. E., & Wilgus, T. A. (2014) · Advances in Wound Care · doi:10.1089/wound.2013.0517 · Cited by 1,169
Nanoparticles and nanofibers for topical drug delivery
Goyal, R., Macri, L. K., Kaplan, H. M., & Kohn, J. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.10.049 · Cited by 591
Greaves, N. S., Ashcroft, K. J., Baguneid, M. S., & Bayat, A. (2013) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2013.07.008 · Cited by 493
Biocompatible Materials for Continuous Glucose Monitoring Devices
Nichols, S. P., Koh, A., Storm, W. L., Shin, J. H., & Schoenfisch, M. H. (2013) · Chemical Reviews · doi:10.1021/cr300387j · Cited by 347
Liu, X., Lee, P., Ho, C., Lui, V. C. H., Chen, Y., Che, C., Tam, P. K. H., & Wong, K. K. (2010) · ChemMedChem · doi:10.1002/cmdc.200900502 · Cited by 336
Metadata
- Authors
- Wu, W.-S., Wang, F.-S., Yang, K. D., Huang, C.-C., & Kuo, Y.-R.
- Affiliations
- Chang Gung University (TW)
- Corresponding author
- Kuo, Yur-Ren
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 126
- Issue
- 6
- Pages
- 1264-1271
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2147641426
- Cited by
- 174
- References
- 34
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 10 · 2023: 6 · 2022: 14 · 2021: 12 · 2020: 9 · 2019: 6 · 2018: 8 · 2017: 8 · 2016: 12 · 2015: 10 · 2014: 7 · 2013: 10 · 2012: 6
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pittsburgh
- National Science Council
- Topics
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Health Sciences › Medicine › Surgery › Vascular Malformations and Hemangiomas
- Keywords
- dexamethasone, glucocorticoid therapy, vascular endothelial growth factor, VEGF-A, keloid fibroblasts, fibroblast proliferation, glucocorticoid receptor, RU486, angiogenesis
- MeSH terms
- Antibodies, Monoclonal, Cells, Cultured, Dexamethasone, Fibroblasts, Glucocorticoids, Humans, Keloid, Receptors, Glucocorticoid, RNA, Messenger, Umbilical Cord, Mifepristone, Vascular Endothelial Growth Factor Receptor-2, Vascular Endothelial Growth Factor A, Endothelial Cells, Cell Proliferation
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
