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Activated Hippo/Yes-Associated Protein Pathway Promotes Cell Proliferation and Anti-apoptosis in Endometrial Stromal Cells of Endometriosis.
J Clin Endocrinol Metab. 2016 04; 101(4):1552-61.JC

Abstract

CONTEXT

The imbalance in cell proliferation and apoptosis is considered an important role in the pathogenesis of endometriosis, but the exact mechanisms remains unclear. A newly established signaling pathway–Hippo/Yes-associated protein (YAP) pathway plays a critical role in the proliferation and apoptosis processes. However, studies focusing on Hippo/YAP pathway and endometriosis are lacking.

OBJECTIVE

The objective was to explore the function of the Hippo/YAP pathway in endometriosis.

SETTING AND DESIGN

The expression of YAP was first investigated in endometrium of women with or without endometriosis. The role of YAP in cell proliferation and apoptosis is identified by transfection of endometrial stromal cells (ESCs) in vitro, subsequent Verteporfin treatments in eutopic ESCs in vitro, and endometriosis animal model of nude mice in vivo.

RESULTS

Our results revealed that increased expression of YAP and decreased expression of p-YAP in ectopic and eutopic endometrium compared with normal endometrium. YAP knockdown in eutopic ESCs decreased cell proliferation and enhanced cell apoptosis companied with decreased expression of TEAD1, CTGF, and B-cell lymphoma/leukemia (BCL)-2; whereas overexpression of YAP resulted in increased proliferation and decreased apoptosis of normal ESCs with increased expression of TEAD1, CTGF, and BCL-2. By chromatin immunoprecipitation qPCR CTGF and BCL-2 were identified as directly downstream target genes of YAP-TEAD1 active complex. Eutopic ESCs treated with Verteporfin revealed decreased proliferation and enhanced apoptosis whereas in endometriosis animal models of nude mice treated with Verteporfin, the size of endometriotic lesions was significantly reduced.

CONCLUSIONS

Our study suggests that the Hippo/YAP-signaling pathway plays a critical role in the pathogenesis of endometriosis and should present a novel therapeutic method against endometriosis.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu Sichuan 610041, People's Republic of China.Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu Sichuan 610041, People's Republic of China.Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu Sichuan 610041, People's Republic of China.Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu Sichuan 610041, People's Republic of China.Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu Sichuan 610041, People's Republic of China.Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu Sichuan 610041, People's Republic of China.Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu Sichuan 610041, People's Republic of China.

Pub Type(s)

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

Language

eng

PubMed ID

26977530

Citation

Song, Yong, et al. "Activated Hippo/Yes-Associated Protein Pathway Promotes Cell Proliferation and Anti-apoptosis in Endometrial Stromal Cells of Endometriosis." The Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 4, 2016, pp. 1552-61.
Song Y, Fu J, Zhou M, et al. Activated Hippo/Yes-Associated Protein Pathway Promotes Cell Proliferation and Anti-apoptosis in Endometrial Stromal Cells of Endometriosis. J Clin Endocrinol Metab. 2016;101(4):1552-61.
Song, Y., Fu, J., Zhou, M., Xiao, L., Feng, X., Chen, H., & Huang, W. (2016). Activated Hippo/Yes-Associated Protein Pathway Promotes Cell Proliferation and Anti-apoptosis in Endometrial Stromal Cells of Endometriosis. The Journal of Clinical Endocrinology and Metabolism, 101(4), 1552-61. https://doi.org/10.1210/jc.2016-1120
Song Y, et al. Activated Hippo/Yes-Associated Protein Pathway Promotes Cell Proliferation and Anti-apoptosis in Endometrial Stromal Cells of Endometriosis. J Clin Endocrinol Metab. 2016;101(4):1552-61. PubMed PMID: 26977530.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activated Hippo/Yes-Associated Protein Pathway Promotes Cell Proliferation and Anti-apoptosis in Endometrial Stromal Cells of Endometriosis. AU - Song,Yong, AU - Fu,Jing, AU - Zhou,Min, AU - Xiao,Li, AU - Feng,Xue, AU - Chen,Hengxi, AU - Huang,Wei, Y1 - 2016/03/15/ PY - 2016/3/16/entrez PY - 2016/3/16/pubmed PY - 2017/6/9/medline SP - 1552 EP - 61 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 101 IS - 4 N2 - CONTEXT: The imbalance in cell proliferation and apoptosis is considered an important role in the pathogenesis of endometriosis, but the exact mechanisms remains unclear. A newly established signaling pathway–Hippo/Yes-associated protein (YAP) pathway plays a critical role in the proliferation and apoptosis processes. However, studies focusing on Hippo/YAP pathway and endometriosis are lacking. OBJECTIVE: The objective was to explore the function of the Hippo/YAP pathway in endometriosis. SETTING AND DESIGN: The expression of YAP was first investigated in endometrium of women with or without endometriosis. The role of YAP in cell proliferation and apoptosis is identified by transfection of endometrial stromal cells (ESCs) in vitro, subsequent Verteporfin treatments in eutopic ESCs in vitro, and endometriosis animal model of nude mice in vivo. RESULTS: Our results revealed that increased expression of YAP and decreased expression of p-YAP in ectopic and eutopic endometrium compared with normal endometrium. YAP knockdown in eutopic ESCs decreased cell proliferation and enhanced cell apoptosis companied with decreased expression of TEAD1, CTGF, and B-cell lymphoma/leukemia (BCL)-2; whereas overexpression of YAP resulted in increased proliferation and decreased apoptosis of normal ESCs with increased expression of TEAD1, CTGF, and BCL-2. By chromatin immunoprecipitation qPCR CTGF and BCL-2 were identified as directly downstream target genes of YAP-TEAD1 active complex. Eutopic ESCs treated with Verteporfin revealed decreased proliferation and enhanced apoptosis whereas in endometriosis animal models of nude mice treated with Verteporfin, the size of endometriotic lesions was significantly reduced. CONCLUSIONS: Our study suggests that the Hippo/YAP-signaling pathway plays a critical role in the pathogenesis of endometriosis and should present a novel therapeutic method against endometriosis. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/26977530/Activated_Hippo/Yes_Associated_Protein_Pathway_Promotes_Cell_Proliferation_and_Anti_apoptosis_in_Endometrial_Stromal_Cells_of_Endometriosis_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2016-1120 DB - PRIME DP - Unbound Medicine ER -