Searching for a good model for systemic sclerosis: the molecular profile and vascular changes occurring in UCD-200 chickens strongly resemble the early phase of human systemic sclerosis
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Submission date: 2014-08-27
Final revision date: 2014-11-17
Acceptance date: 2014-12-02
Online publication date: 2016-07-01
Publication date: 2016-06-30
Arch Med Sci 2016;12(4):828-843
Introduction: Vascular injury and endothelial cell (EC) apoptosis are the earliest events in systemic sclerosis (SSc), before the onset of fibrosis, and stromal cell-derived factor 1 (SDF-1), vascular endothelial growth factor (VEGFA), endothelin-1 (ET-1) and platelet-derived growth factors (PDGF-BB) represent the key molecules to study the link between vascular injury and fibrosis during SSc. The University of California at Davis line 200 (UCD-200) chickens display the same hallmarks of human SSc: vascular occlusion, perivascular lymphocytic infiltration and fibrosis of skin and internal organs. In this study we assessed both cytokines and growth factors involved in the early phases of the UCD-200 chickens’ skin lesions, to determine whether these animals might represent an appropriate experimental model to study the pathogenesis of SSc.
Material and methods: Immunofluorescence analysis was performed on human SSc skin, human healthy control (hHC) skin, UCD-200 combs and HC H.B15 chicken (cHC) combs, using anti-SDF-1, CXCR4, VEGFA, VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2), ET-1, ET receptor A (ETAR), ET receptor B (ETBR), PDGF-BB, and PDGF receptor (PDGFR) antibodies. The plasma concentrations of SDF-1, VEGFA, ET-1 and PDGF-BB were determined by ELISA.
Results: All the molecules analyzed showed higher levels in SSc patients and UCD-200 chickens than in hHC and cHC. Furthermore, the levels of the assessed molecules paralleled the severity of comb involvement.
Conclusions: The molecular similarities between avian and human SSc, observed in this study, suggest that the UCD-200 chickens are an interesting model for translational approaches to SSc.
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