Insulin-like growth factor I promotes adipogenesis in hemangioma stem cells from infantile hemangiomas

Infantile hemangiomas (IH) are the most common infantile neoplasms and are characterized by initial proliferation during infancy and subsequent spontaneous regression within the next 5-10 years, frequently leaving fibrous fat residues. However, the specific mechanisms underlying the differentiation of hemangioma stem cells (HemSCs) into adipocytes are not clear. The purpose of the present study was to investigate the effect of insulin-like growth factor I (IGF-1) on HemSCs from patients with IH and to determine the signaling mechanisms involved. Treatment of HemSCs with IGF-1 led to upregulation of the protein expression levels of peroxisome proliferator-activated receptor- (PPAR). By contrast, inhibition of the IGF-1 receptor (IGF-1R) or phosphoinositide 3-kinase (PI3K) activity decreased the expression of PPAR, in addition to that of CCAAT/enhancer-binding protein (C/EBP), C/EBP, and adiponectin. IGF-1 upregulated the expression of phosphorylated RAC- serine/threonine-protein kinase in IH cells, whereas a specific PI3K inhibitor or IGF-1R antibody blocked this effect. These results indicated that IGF-1 is a pro-proliferative and pro-lipogenic factor in IH HemSCs. Taken together, these findings indicated that IGF-1 is able to upregulate PPAR by activating the IGF-1R and PI3K pathways, thereby accelerating lipogenesis and enhancing IH HemSC adipogenesis.