Aetiopathogenesis
Dickkopf-1 is downregulated early and universally in the skin of patients with systemic sclerosis despite normal circulating levels
D. Daoussis1, D.J. Papachristou2, T. Dimitroulas3, T. Sidiropoulos4, I. Antonopoulos5, A.P. Andonopoulos6, S.-N. Liossis7
- Department of Rheumatology, Patras University Hospital, University of Patras Medical School, Patras, Greece. jimdaoussis@hotmail.com
- Department of Anatomy-Histology-Embryology, Laboratory of Bone and Soft Tissue Studies, University of Patras Medical School, Greece.
- 4th Department of Internal Medicine Hippokration Hospital, Medical School, Aristotle University of Thessaloniki, Greece.
- Hospital of Skin and Venereal Diseases, Thessaloniki, Greece.
- Department of Rheumatology, Patras University Hospital, University of Patras Medical School, Greece.
- Department of Rheumatology, Patras University Hospital, University of Patras Medical School, Greece.
- Department of Rheumatology, Patras University Hospital, University of Patras Medical School, Greece.
CER11416
2018 Vol.36, N°4 ,Suppl.113
PI 0045, PF 0049
Aetiopathogenesis
Free to view
(click on article PDF icon to read the article)
PMID: 30277866 [PubMed]
Received: 23/05/2018
Accepted : 28/08/2018
In Press: 28/09/2018
Published: 28/09/2018
Abstract
OBJECTIVES:
The activity of the Wnt pathway, a critical mediator of fibrosis, is regulated by Dickkopf-1 (Dkk-1). Dkk-1 is absent from scleroderma skin in contrast to skin from healthy subjects where it is clearly expressed. There are no data on circulating levels and function of Dkk-1 in patients with systemic sclerosis (SSc). Our objectives are to assess: i) circulating and functional levels of Dkk-1 in patients with SSc and ii) whether the striking lack of Dkk-1 skin expression is also evident in a) clinically uninvolved skin from patients with SSc and b) very early disease prior to skin thickening.
METHODS:
Circulating Dkk-1 levels were measured in 50 patients with SSc and 50 controls. Skin biopsies were obtained from SSc patients from a) clinically involved skin b) clinically uninvolved skin, c) oedematous skin prior to skin thickening.
RESULTS:
Circulating and functional Dkk-1 levels were similar in patients with SSc and controls. Healthy skin displayed a high Dkk-1 immuno-expression in the epidermis and dermal fibroblasts in contrast to clinically involved scleroderma skin where Dkk-1 was totally absent. In all biopsies of clinically uninvolved skin Dkk-1 was only moderately expressed whereas skin from very early disease displayed only a weak Dkk-1 immunoreactivity.
CONCLUSIONS:
The downregulation of Dkk-1 at the oedematous phase of the disease indicates that the Wnt pathway is involved early in the disease process and may play a role in driving fibrosis. The decrease in Dkk-1 expression in clinically uninvolved scleroderma skin indicates that skin in SSc is universally affected.
