Kofi 2012-08-08 04:00:17
Br J Dermatol. 2010 Nov 11
Vitamin D: a novel therapeutic approach for keloid, an in vitro analysis.
Zhang GY, Cheng T, Luan Q, Liao T, Nie CL, Zheng X, Xie XG, Gao WY.
Department of Hand and Plastic Surgery, the 2nd Affiliated Hospital of
Wenzhou Medical College, Wenzhou, Zhejiang Province, China Department of
Dermatology, University of Lubeck, Lubeck, Germany Department of
Orthopaedic Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiao
Tong University School of Medicine, Shanghai, China Department of
Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an,
Shaanxi Province, China Department of Otolaryngology, Head and Neck
surgery, Charite Campus Benjamin Franklin, Berlin Germany Department of
Head and Neck Surgery, The Third Affiliated Hospital of Harbin Medical
University, Harbin, China.
Background Vitamin D and its metabolites play an important role in
calcium homeostasis; bone remodeling, hormone secretion, cell
proliferation, and differentiation. Recent studies also suggest a
beneficial role of vitamin D in slowing the progression of tissue
fibrosis. However their effects on dermal fibrosis-keloid are unknown.
Objective To investigate the effect of 1, 25-dihydroxyvitamin D3 (1,25D)
in the pathogenesis of tissue fibrosis by keloid fibroblasts. Methods
Keloid fibroblasts were cultured and exposed to a different
concentration 1,25D in the absence or presence of transforming growth
factor (TGF-beta1). Keloid fibroblasts phenotypes and protein production
were analyzed by real-time reverse transcriptase-polymerase chain
reaction, Western blot, and immunofluorescence and multiplexed
enzymelinked immunosorbent assay techniques. Collagen synthesis was
evaluated by measuring (3) H-proline incorporation. The effect of 1,25D
on cell proliferation and viability was evaluated by Formazan assay,
PCNA antigen expression and the colorimetric conversion of 3-[4,
5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide. Results We
confirmed the presence of vitamin D receptors (VDRs) in cultured keloid
fibroblasts. Fibroblasts transfected with a vitamin D response element
reporter construct and exposed to the active vitamin D metabolite,
1,25D, showed increased promoter activity indicating VDR functionality
in these cells. Incubation of keloid fibroblasts with 1,25D suppressed
TGF-beta1 induced collagen type I, fibronectin and alpha-smooth muscle
actin expression. 1,25D also modulated plasminogen activator inhibitor-1
(PAI-1) and matrix metallopeptidase (MMP-9) expression induced by
TGF-beta1. Interestingly, 1,25D induced hematopoietic growth factor
(HGF) mRNA expression and protein secretion in keloid fibroblasts.
Conclusions This study highlights key mechanistic pathways through which
vitamin D decreases fibrosis, and provides a rationale for studies to
test vitamin D supplementation as a preventive and/or early treatment
strategy for keloid and related fibrotic disorders. Copyright (c) 2010
British Association of Dermatologists.