TGF-1 inhibits microvascular-like formation by decreasing VCAM1 and ICAM1 via the upregulation of SNAIL in human granulosa cells
文献类型： 外文期刊
作者： Li, Hui 1 ; Chang, Hsun-Ming 2 ; Lin, Yung-Ming 2 ; Shi, Zhendan 1 ; Leung, Peter C. K. 2 ;
作者机构： 1.Jiangsu Acad Agr Sci, Inst Anim Sci, Key Lab Anim Breeding & Reprod, Nanjing 210014, Peoples R China
2.Univ British Columbia, BC Childrens Hosp Res Inst, Dept Obstet & Gynaecol, Room 317,950 West 28th Ave, Vancouver, BC V5Z 4H4, Canada
3.Jiangsu Acad Agr Sci, Jiangsu Key Lab Food Qual & Safety, State Key Lab Cultivat Base, Minist Sci & Technol, Nanjing 210014, Peoples R China
关键词： Granulosa cell; TGF-beta 1; SNAIL; VCAM1; ICAM1; Angiogenesis
期刊名称：MOLECULAR AND CELLULAR ENDOCRINOLOGY （ 影响因子：4.102； 五年影响因子：4.226 ）
ISSN： 0303-7207
年卷期： 2021 年 535 卷
页码：
收录情况： SCI
摘要： Three major endothelial cell junctional adhesion molecules (VCAM1, ICAM1 and E-SELECTIN) play important roles in the process of angiogenesis, a progression of extensive physiological vascularization that occurs during the formation of the corpus luteum. Our previous studies demonstrated that TGF-beta 1 is a negative regulator of luteinization and progesterone production in luteinized human granulosa (hGL) cells. Whether TGF-beta 1 can regulate the expression of these endothelial cell adhesion molecules and subsequent angiogenesis in hGL cells remains to be elucidated. Using dual inhibition approaches (small molecular inhibitors and siRNA-based knockdown), we provided the first data showing that TGF-beta 1 significantly upregulates the expression of the SNAIL transcription factor, which in turn suppresses the expression of VCAM1 and ICAM1 in hGL cells. Additionally, we demonstrate that the suppressive effects on the expression of VCAM1 and ICAM1 induced by TGF-beta 1 treatment were most likely via an ALK5-mediated SMAD-dependent signaling pathway. Furthermore, functional studies showed that hGL cells cultured on Matrigel exhibited two typical endothelial cell phenotypes, microvascular-like formation and a sprouting microvascular pattern. Notably, these phenotypes were significantly suppressed by either TGF-beta 1 treatment or knockdown of VCAM1 and ICAM1. Our findings suggest that TGF-beta 1 plays a potential role in the inhibition of granulosa cell angiogenesis by downregulating the expression of VCAM1 and ICAM1 during follicular development and corpus luteum formation.
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