Insulin‑like growth factor 2 promotes the adipogenesis of hemangioma‑derived stem cells

Zhang,Kui; Wang,Fan; Huang,Jun; Lou,Yin; Xie,Juan; Li,Honghong; Cao,Dongsheng; Huang,Xueying

doi:10.3892/etm.2018.7132

Insulin‑like growth factor 2 promotes the adipogenesis of hemangioma‑derived stem cells

Authors:
- Kui Zhang
- Fan Wang
- Jun Huang
- Yin Lou
- Juan Xie
- Honghong Li
- Dongsheng Cao
- Xueying Huang
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Affiliations: Department of Plastic Surgery, The Second Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China, Department of Anesthesia, The Second Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China, Department of Anatomy, Anhui Medical University, Hefei, Anhui 230031, P.R. China
Published online on: December 24, 2018 https://doi.org/10.3892/etm.2018.7132
Pages: 1663-1669
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

Infantile hemangioma (IH), which is the most common tumor in infants, is characterized by rapid proliferation followed by spontaneous regression into fibro‑fatty tissue in childhood. However, its specific mechanism has not been clarified. Our previous studies showed that insulin‑like growth factor 2 (IGF‑2) is increased in the proliferative phase of IH, which is deemed to form from hemangioma‑derived stem cells (HemSC). However, it remains unclear whether IGF‑2 can promote the adipogenic differentiation of HemSCs and the signaling mechanisms involved require further elucidation. In the present study, CCK-8 assay was used to detect the effect of different concentrations of IGF-2 on the proliferation of HemSCs. Immunohistochemistry was applied to observe the expression of IGF-2 and its receptors in cells. Oil red o-staining of adipogenesis was conducted after cells recevied no treatment or were induced with IGF-2 or IGF-2 plus OSI-906 for 10 days. Cells were cultured in EGM-2/FBS-10% alone or containing IGF-2, IGF-2 plus OSI-906 or IGF-2 plus LY294002 and the protein expression of C/EBPα, C/EBPβ, PPARγ, adiponectin, p-AKT and total AKT was determined using western blot analysis. In another experiment, cells were treated with 25, 50 or 100 μM propranolol, or vehicle. C/EBPα, C/EBPβ, PPARγ and IGF-2 were analyzed using western blot analysis or reverse transcription-quantitative polymerase chain reaction. Results indicated that IGF‑2 significantly promoted the cell proliferation and lipid accumulation of HemSCs. The expression of phosphorylated AKT (p‑AKT), C/EBPα, C/EBPβ, PPARγ and adiponectin was increased in IGF‑2‑treated HemSCs culture, whereas these changes were repressed by the inhibition of either the IGF‑1 receptor (IGF‑1R) or phosphoinositide 3‑kinase (PI3K). Our previous research showed that propranolol accelerated adipogenesis in HemSCs and induced the upregulation of IGF‑2. The results of the present study indicate that IGF‑2 is able to accelerate adipogenesis, and the propranolol‑induced promotion of dysregulated adipogenesis may be mediated by the IGF‑2 via IGF‑1R and PI3K pathways.

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