In:
Experimental Dermatology, Wiley, Vol. 24, No. 2 ( 2015-02), p. 127-132
Abstract:
CCN 1 is a pleiotropic molecule involved in angiogenesis and postnatal vasculogenesis, both of which are impaired in systemic sclerosis ( SS c). To elucidate the potential role of CCN 1 in the development of SS c, we investigated CCN 1 expression in the lesional skin of SS c patients and SS c animal models and the clinical correlation of serum CCN 1 levels. CCN 1 expression was markedly decreased in dermal small blood vessels of SS c patients compared with those of healthy controls, while comparable between normal and SS c dermal fibroblasts. Transcription factor Fli1, whose deficiency due to epigenetic suppression is implicated in the pathogenesis of SS c, occupied the CCN 1 promoter and gene silencing of Fli1 resulted in the reduction of CCN 1 expression in human dermal microvascular endothelial cells. Consistently, CCN 1 expression was suppressed uniformly and remarkably in dermal blood vessels of Fli1 +/− mice and partially in those of endothelial cell‐specific Fli1 knockout mice. Furthermore, serum CCN 1 levels were significantly decreased in SS c patients with previous and current history of digital ulcers as compared to those without. Collectively, these results suggest that endothelial CCN 1 downregulation at least partially due to Fli1 deficiency may contribute to the development of digital ulcers in SS c patients. This study further supports the idea that epigenetic downregulation of Fli1 is a potential predisposing factor in the pathogenesis of SS c.
Type of Medium:
Online Resource
ISSN:
0906-6705
,
1600-0625
DOI:
10.1111/exd.2015.24.issue-2
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2026228-0
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