Epidermal Growth Factor Like-domain 7 and miR-126 are abnormally expressed in diffuse Systemic Sclerosis fibroblasts.
Vasiliki LiakouliPaola CiprianiPaola Di BenedettoNoemi PanzeraPiero RuscittiIlenia PantanoOnorina BerardicurtiFrancesco CarubbiFilomena EstevesGeorgia MavriaFrancesco Del GaldoRoberto GiacomelliPublished in: Scientific reports (2019)
Systemic sclerosis (SSc) is characterized by microangiopathy with impaired reparative angiogenesis and fibrosis. Epidermal Growth Factor Like-domain 7 (EGFL7), firstly described in endothelial cells plays a pivotal role in angiogenesis. Fibroblasts (FBs) are involved in vascular remodeling, under physiological and pathological conditions. In this study, we investigated: (i) the expression of EGFL7 and its miR-126 in patients affected by diffuse cutaneous SSc (dcSSc); (ii) the ability of Transforming Growth Factor-beta (TGF-β) to modulate EGFL7 expression; (iii) the ability of EGFL7 to modulate COL1A1 expression and proliferation/migration, and (iv) the functional role of EGFL7 on angiogenesis. Patients were divided in 2 subsets: patients fulfilling the classification criteria in less than one year from Raynaud's Phenomenon onset (Early Onset Subset-EOS), and all the others (Long Standing Subset-LSS). We show that EGFL7 expression is increased in EOS dcSSc skin and cultured FBs. EGFL7 is inducible by TGF-β on Healthy Controls (HC) FBs but not in SSc-FBs. EGFL7 decreases COL1A1 expression in EOS SSc-FBs while EGFL7 silencing up-regulates COL1A1 expression. EGFL7 promotes migration/invasion of EOS SSc-FBs but not proliferation. Finally, SSc-FBs, partially inhibit angiogenesis in organotypic coculture assays, and this is reversed by treatment with human recombinant (rh)EGFL7. We conclude that EGFL7 and its specific microRNA miR-126 may be involved in the pathogenesis of SSc vasculopathy and fibrosis.
Keyphrases
- endothelial cells
- systemic sclerosis
- poor prognosis
- growth factor
- end stage renal disease
- transforming growth factor
- early onset
- long non coding rna
- ejection fraction
- newly diagnosed
- chronic kidney disease
- cell proliferation
- interstitial lung disease
- prognostic factors
- wound healing
- peritoneal dialysis
- epithelial mesenchymal transition
- vascular endothelial growth factor
- machine learning
- patient reported outcomes
- signaling pathway
- low grade
- high throughput
- late onset
- long noncoding rna
- high grade
- smoking cessation