Pigment epithelium derived factor inhibits the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro

Yanmei Sun; Xuan Che; Libo Zhu; Mengdan Zhao; Guofang Fu; Xiufeng Huang; Hong Xu; Fuqiang Hu; Xinmei Zhang

doi:10.1371/journal.pone.0045223

Pigment epithelium derived factor inhibits the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro

PLoS One. 2012;7(9):e45223. doi: 10.1371/journal.pone.0045223. Epub 2012 Sep 18.

Authors

Yanmei Sun¹, Xuan Che, Libo Zhu, Mengdan Zhao, Guofang Fu, Xiufeng Huang, Hong Xu, Fuqiang Hu, Xinmei Zhang

Affiliation

¹ Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

Abstract

Angiogenesis is a prerequisite for the formation and development of endometriosis. Pigment epithelium derived factor (PEDF) is a natural inhibitor of angiogenesis. We previously demonstrated a reduction of PEDF in the peritoneal fluid, serum and endometriotic lesions from women with endometriosis compared with women without endometriosis. Here, we aim to investigate the inhibitory effect of PEDF on human endometriotic cells in vivo and in vitro. We found that PEDF markedly inhibited the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro by up-regulating PEDF expression and down-regulating vascular endothelial growth factor (VEGF) expression. Moreover, apoptotic index was significantly increased in endometriotic lesions in vivo and endometriotic stromal cells in vitro when treated with PEDF. In mice treated with PEDF, decreased microvessel density labeled by Von Willebrand factor but not by α-Smooth Muscle Actin was observed in endometriotic lesions. And it showed no increase in PEDF expression of the ovary and uterus tissues. These findings suggest that PEDF gene therapy may be a new treatment for endometriosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / genetics
Actins / metabolism
Adult
Animals
Apoptosis / drug effects
Endometriosis / drug therapy*
Endometriosis / genetics
Endometriosis / metabolism
Endometriosis / pathology
Endometrium / blood supply*
Endometrium / drug effects*
Endometrium / pathology
Eye Proteins / pharmacology*
Female
Gene Expression Regulation / drug effects
Humans
Mice
Mice, Nude
Microvessels / drug effects
Neovascularization, Pathologic
Nerve Growth Factors / pharmacology*
Ovary / cytology
Ovary / drug effects
Ovary / metabolism
Serpins / pharmacology*
Stromal Cells / drug effects
Stromal Cells / metabolism
Stromal Cells / pathology
Transplantation, Heterologous
Vascular Endothelial Growth Factor A / antagonists & inhibitors
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism
von Willebrand Factor / genetics
von Willebrand Factor / metabolism

Substances

Actins
Eye Proteins
Nerve Growth Factors
Serpins
Vascular Endothelial Growth Factor A
alpha-smooth muscle actin, mouse
pigment epithelium-derived factor
vascular endothelial growth factor A, mouse
von Willebrand Factor

Grants and funding

The authors appreciate the financial support of the National Nature Science Foundation of China (81070468, 81173000 and 30873174) and the Nature Science Foundation of Zhejiang province (Y2090336 and z207489). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.