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Article Dans Une Revue Journal of Investigative Dermatology Année : 2020

Decreased CCN3 in Systemic Sclerosis Endothelial Cells Contributes to Impaired Angiogenesis

François Picard
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Thierry Schaeverbeke

Résumé

Systemic sclerosis (SSc) is a rare and severe connective tissue disease combining autoimmune and vasculopathy features, ultimately leading to organ fibrosis. Impaired angiogenesis is an often silent and life-threatening complication of the disease. We hypothesize that CCN3, a member of the CCN family of extracellular matrix proteins, which is an antagonist of the profibrotic protein CCN2 as well as a proangiogenic factor, is implicated in SSc pathophysiology. We performed skin biopsies on 26 patients with SSc, both in fibrotic and nonfibrotic areas for 17 patients, and collected 18 healthy control skin specimens for immunohistochemistry and cell culture. Histological analysis of nonfibrotic and fibrotic SSc skin shows a systemic decrease of papillary dermis surface as well as disappearance of capillaries. CCN3 expression is systematically decreased in the dermis of patients with SSc compared with healthy controls, particularly in dermal blood vessels. Moreover, CCN3 is decreased in vitro in endothelial cells from patients with SSc. We show that CCN3 is essential for endothelial cell migration and angiogenesis in vitro. In conclusion, CCN3 may represent a promising therapeutic target for patients with SSc presenting with vascular involvement.
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Dates et versions

hal-03490222 , version 1 (21-06-2022)

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Paternité - Pas d'utilisation commerciale

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Pauline Henrot, François Moisan, Paôline Laurent, Pauline Manicki, Priscilla Kaulanjan-Checkmodine, et al.. Decreased CCN3 in Systemic Sclerosis Endothelial Cells Contributes to Impaired Angiogenesis. Journal of Investigative Dermatology, 2020, 140, pp.1427 - 1434.e5. ⟨10.1016/j.jid.2019.11.026⟩. ⟨hal-03490222⟩

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