Cited by 174Dermatologic Treatments and ResearchWound Healing and TreatmentsVascular Malformations and Hemangiomas

Dexamethasone Induction of Keloid Regression through Effective Suppression of VEGF Expression and Keloid Fibroblast Proliferation

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Wu, Wen-Sheng, Wang, Feng-Sheng, Yang, Kuender D., Huang, Chao-Cheng, Kuo, Yur-Ren·2006·Journal of Investigative Dermatology

Abstract

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.

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Crossref · 10.1038/sj.jid.5700274

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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
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 › Rehabilitation › 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

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