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Background <p>As the first-line treatment for hemangioma (IH), the mechanism of propranolol (PRN) remains unclear. In clinical practice, challenges such as PRN resistance and rebound after discontinuation of PRN are frequently encountered. Hence, this research seeks to investigate the mechanisms underlying PRN-induced regression of IH.</p> Methods <p>Hexokinase 2 (HK2) expression was assessed via immunohistochemistry and double-labeling staining. Glycolysis in hemangioma-derived stem cells (HemSCs) was evaluated by measuring glucose uptake, lactate, and ATP production. Peroxisome proliferator-activated receptor Gamma (PPARγ) and vascular endothelial cadherin (VE-cadherin) levels were analyzed using Western blot and qPCR. PRN-treated HemSCs were examined for adipogenic differentiation via Oil Red O and BODIPY staining.</p> Results <p>Our results demonstrate that PRN inhibits HemSCs proliferation and endothelial differentiation while promoting adipogenesis by suppressing glycolysis. This effect occurs through HK2 downregulation, likely mediated by PI3K-Akt pathway inhibition. Notably, HK2 expression was significantly lower in CD133<sup>+</sup> cells from involutive hemangiomas versus proliferative lesions.</p> Conclusions <p>This study presents the first evidence for the essential role of glycolysis in regulating the proliferation and differentiation of HemSCs, while the efficiency of PRN may be associated with the inhibition of HK2-mediated glycolysis in HemSCs by suppressing the activities of PI3K-Akt pathway.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Glycolysis level is high in HemSCs.</p> </ItemContent> <ItemContent> <p>Glycolysis is required in propranolol perturbated the HemSCs differentiation.</p> </ItemContent> <ItemContent> <p>PRN could inhibit glycolysis of HemSCs through down-regulation of HK2 expression.</p> </ItemContent> <ItemContent> <p>PRN suppressed endothelial differentiation and accelerated adipogenesis of HemSCs.</p> </ItemContent> <ItemContent> <p>PRN down-regulated HK2 expression through restrained the PI3k-Akt pathway.</p> </ItemContent> </UnorderedList></p> <p></p>

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Propranolol accelerates adipogenesis and inhibits endothelium differentiation of HemSCs via suppressing HK2 mediated glycolysis

  • 期刊论文

  • 发表日期：

    2025年5月17日

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  • Tianshuang Zhu,
  • Peipei Wang,
  • Rong Wang,
  • Guoyong Tong,
  • Yu Sun,
  • Shaodong Yang,
  • Xiaoshun Zhou,
  • Dongsheng Mou,
  • Wenqun Zhong,
  • Yu Cai

摘要

Background

As the first-line treatment for hemangioma (IH), the mechanism of propranolol (PRN) remains unclear. In clinical practice, challenges such as PRN resistance and rebound after discontinuation of PRN are frequently encountered. Hence, this research seeks to investigate the mechanisms underlying PRN-induced regression of IH.

Methods

Hexokinase 2 (HK2) expression was assessed via immunohistochemistry and double-labeling staining. Glycolysis in hemangioma-derived stem cells (HemSCs) was evaluated by measuring glucose uptake, lactate, and ATP production. Peroxisome proliferator-activated receptor Gamma (PPARγ) and vascular endothelial cadherin (VE-cadherin) levels were analyzed using Western blot and qPCR. PRN-treated HemSCs were examined for adipogenic differentiation via Oil Red O and BODIPY staining.

Results

Our results demonstrate that PRN inhibits HemSCs proliferation and endothelial differentiation while promoting adipogenesis by suppressing glycolysis. This effect occurs through HK2 downregulation, likely mediated by PI3K-Akt pathway inhibition. Notably, HK2 expression was significantly lower in CD133+ cells from involutive hemangiomas versus proliferative lesions.

Conclusions

This study presents the first evidence for the essential role of glycolysis in regulating the proliferation and differentiation of HemSCs, while the efficiency of PRN may be associated with the inhibition of HK2-mediated glycolysis in HemSCs by suppressing the activities of PI3K-Akt pathway.

Impact

Glycolysis level is high in HemSCs.

Glycolysis is required in propranolol perturbated the HemSCs differentiation.

PRN could inhibit glycolysis of HemSCs through down-regulation of HK2 expression.

PRN suppressed endothelial differentiation and accelerated adipogenesis of HemSCs.

PRN down-regulated HK2 expression through restrained the PI3k-Akt pathway.