146 N-myc downstream regulated gene 1 (NDRG1) promotes adipocyte differentiation in infantile hemangioma endothelial cells

Abstract

Infantile hemangioma (IH) is the most common vascular tumor of infancy, characterized by a rapid growth phase followed by a spontaneous involution to adipose and fibrous tissue over time. However, the mechanism of pathogenesis in IH involution is still unknown. N-myc downstream regulated gene 1(NDRG1) is recently known to regulate adipocyte differentiation through down regulation of suppressor genes TGF-β, as well as induction of terminal differentiation markers. Here, we evaluated the role of NDRG1 during differentiation from hemangioma endothelial cells (HemEC) to adipocytes. We found that NDRG1 expression in HemEC derived from IH tissues was upregulated during proliferating phase and downregulated during involution. NDRG1 was identified as a significant regulator of HemEC differentiation. Loss-of function analysis using siRNA mediated knockdown of NDRG1 demonstrated inhibition of adipogenesis. NDRG1 knockdown decreased stem-like properties of HemEC in IH including induced pluripotent stem cell factors such as C-MYC. Taken together, we showed a functional role for NDRG1 in promotion of multipotent hemangioma derived endothelial cells to the adipocytes