Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Παρασκευή 7 Δεκεμβρίου 2018

A potential contribution of trappin‐2 to the development of vasculopathy in systemic sclerosis

Abstract

Background

Trappin‐2/pre‐elafin is an endogenous inhibitor of human neutrophil elastase involved in inflammation, innate immunity and vascular remodeling, which consist of the complex pathological process of systemic sclerosis (SSc).

Objectives

To clarify the potential role of trappin‐2 in SSc.

Methods

Serum trappin‐2 levels were determined by enzyme‐linked immunosorbent assay in 51 SSc and 18 healthy subjects. Trappin‐2 expression was evaluated in SSc lesional skin and cultured endothelial cells treated with FLI1 siRNA by immunohistochemistry, reverse transcript‐real time PCR and/or immunoblotting. Fli1 binding to the PI3 promoter was assessed by chromatin immunoprecipitation.

Results

Since serum trappin‐2 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction, SSc patients with normal renal function were analyzed. Although serum trappin‐2 levels were comparable between diffuse cutaneous SSc, limited cutaneous SSc and control subjects, the prevalence of digital ulcers or elevated right ventricular systolic pressure (RVSP) was significantly higher in SSc patients with elevated serum trappin‐2 levels than in those with normal levels. Furthermore, serum trappin‐2 levels were significantly increased in SSc patients with digital ulcers or elevated RVSP compared to those without. Moreover, serum trappin‐2 levels positively correlated with RVSP values in SSc patients. Importantly, trappin‐2 expression was enhanced in small vessels of SSc lesional skin. In cultured endothelial cells, trappin‐2 expression was elevated by gene silencing of FLI1 at mRNA and protein levels and Fli1 occupied the PI3 promoter.

Conclusions

Endothelial trappin‐2 up‐regulation partially due to Fli1 deficiency can be associated with the development of SSc vasculopathy.

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