Is Netrin-1 Associated with the Development of Fibrosis in Systemic Sclerosis?

Abstract

AbstractBackgroundNetrin-1 is a laminin class protein that guides the axonal during the first embryonic development, has pushing and pulling properties, and has axonal chemoattractant activity. Netrin-1 has been shown to increase the effect of fibrosis in mouse lung and human SSc lung cell cultures. In this study, we aimed to investigate the relationship between Netrin-1 and Systemic sclerosis (SSc) and to emphasize the role of Netrin-1 in the pathophysiology of SSc by increasing the known VEGF and M2 macrophage expression, which supports the fibrotic process.MethodsThe study included 56 SSc patients with a mean age of 48·.08±13.59 years and 58 healthy volunteers with a mean age of 48.01±11.59 years. SSc organ involvements were scanned retrospectively from patient files, and patients were grouped according to SSc complications. Calculation of Netrin-1 levels was performed using a quantitative sandwich enzyme immunoassay method with an ELISA kit (Elabscience, Texas, USA; catalog number: E-EL-H2328; lot number: GZWTKZ5SWK). The modified Rodnan skin score (mRSS) was used for skin thickness scoring in SSc patients.ResultsThe median value of Netrin-1 was found to be significantly higher in SSc (268.8 [82.75-1006.64]) than in controls (108.63 [21.02-351.49]) (p<0.0001). In ROC analysis, a cut-off value of 354.24 for Netrin in SSc was found to provide a sensitive confidence interval with 32.8% sensitivity and 98.3% specificity (AUC[95% CI]: 0.746-0.895, p<0.0001). There was no significant correlation between Netrin-1 level, organ involvement in SSc, and mRSS (p>0.05).ConclusionWe found a significant relationship between Netrin-1 levels and SSc disease in this study. Our study is the first clinical study in which Netrin-1 elevation was demonstrated in SSc patients.