Page 12 - G. Cell differentiation. division. and death
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[G. Cell differentiation, division, and death-9]
Silk sericin and 4-hexylresorcinol differentiate endothelial
cells via different mechanism in diabetic model
Yei-Jin Kang¹, Seong-Gon Kim¹
¹Oral and Maxillofacial Surgery, Gangneung-Wonju National University, Gangneung 25457, Korea
4-hexyl resorcinol (4HR) elevates vascular endothelial growth factor (VEGF) in RAW264.7 cells via hypoxia inducible
factor (HIF) independent pathway. As endothelial cells are important in angiogenesis, we treated the human umbilical
vein endothelial cells (HUVECs) with 4HR and investigated protein expressional changes by immunoprecipitation
high-performance liquid chromatography (IP-HPLC) using 96 antisera. Here, we found that 4HR upregulated
transforming growth factor-βs (TGF-βs)/SMADs/ vascular endothelial growth factors (VEGFs) signaling, RAF-B/ERK
and p38 signaling, and M2 macrophage polarization pathways. 4HR also increased expression of caspases and
subsequent cellular apoptosis. Knockdown with small interfering RNA (siRNA) targeting to TGF-β1 and the selective
chemical inhibition (A83-01) to ALK5 confirmed the involvement of TGF-β signaling pathway in the 4-HR mediated
VEGFs expression. Mechanistically, 4HR increased TGF-β1 production and subsequent activation of SMADs/VEGFs,
RAF-B/ERK and p38 signaling, and M2 macrophage polarization. 4HR application on burn model of diabetic rats
demonstrated increased level of angiogenic proteins with active capillary regeneration and wound healing.
Collectively, 4HR activates TGF-βs/SMADs/VEGFs signaling in endothelial cells.
