Increased Expression of TGF-beta 1 by 4-hexylresorcinol Is Mediated by Endoplasmic Reticulum and Mitochondrial Stress in Human Umbilical Endothelial Vein Cells

In our previous study, 4-hexylresorcinol (4HR) increased the expression level of vascular endothelial growth factor in human umbilical vein endothelial cells (HUVECs) via the transforming growth factor-beta 1 (TGF-beta 1)-mediated pathway. Endoplasmic reticulum (ER) and mitochondrial stress is a positive regulator of cellular differentiation. As TGF-beta 1 is a master regulator for cellular differentiation, 4HR treatment may increase TGF-beta 1 expression via ER stress. In this study, HUVECs were treated using 4HR (1-100 mu M) for 24 h. The 4HR treatment increased ER stress-associated markers and mitochondrial stress. Increased TGF-beta 1 expression by 4HR administration was alleviated by tauroursodeoxycholate (ER stress inhibitor) treatment. Combining these activities with the elevated acetylation level of histone 3 (H3) by 4HR treatment, TGF-beta 1 expression was increased in HUVECs. Overall, 4HR increased TGF-beta 1 expression through upregulation of the stress response of ER as well as H3 acetylation in HUVECs.