Estrogen receptor beta promotes endometriosis progression by upregulating CD47 expression in ectopic endometrial stromal cells

Laihua Hu; Jinghe Zhang; Yichen Lu; Binqing Fu; Weiping Hu

doi:10.1016/j.jri.2022.103513

Estrogen receptor beta promotes endometriosis progression by upregulating CD47 expression in ectopic endometrial stromal cells

J Reprod Immunol. 2022 Jun:151:103513. doi: 10.1016/j.jri.2022.103513. Epub 2022 Mar 14.

Authors

Laihua Hu¹, Jinghe Zhang¹, Yichen Lu¹, Binqing Fu², Weiping Hu³

Affiliations

¹ Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230036, China; Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center, University of Science and Technology of China, Hefei, Anhui 230001, China.
² Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230036, China; Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center, University of Science and Technology of China, Hefei, Anhui 230001, China. Electronic address: fbq@ustc.edu.cn.
³ Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230036, China; Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center, University of Science and Technology of China, Hefei, Anhui 230001, China. Electronic address: syhwp@163.con.

PMID: 35305523
DOI: 10.1016/j.jri.2022.103513

Abstract

Endometriosis is a common estrogen-dependent gynecological disorder that is characterized by endometrial-like tissue being found at extrauterine sites. Aberrant expression and activation of estrogen receptor beta (ERβ) in ectopic endometrium are involved in endometriosis development. Here, we used primary tissues and cells from endometriosis patients to investigate the molecular mechanisms involved in ERβ's contribution to endometriosis progression. Through RNA-seq, quantitative PCR, and immunohistochemistry analysis, we found that ERβ expression is related to the severity of endometriosis; specifically, the ratio of ESR2/ESR1 in ectopic tissues was positively correlated with the severity of endometriosis, which suggests that ERβ has a predominant role in endometriosis progression. Furthermore, we found that ERβ could bind to the CD47 promoter, increasing CD47 expression levels. CD47 is a critical molecule in "don't eat me" signaling. These data highlight the importance of the ERβ-CD47 axis in the pathogenesis of endometriosis. We believe targeting CD47 may be a novel therapeutic approach for treating endometriosis and other ERβ-associated diseases.

Keywords: CD47; Don’t eat me; ERβ; Endometriosis; Stromal cells.

MeSH terms

CD47 Antigen / genetics
CD47 Antigen / metabolism
Endometriosis* / pathology
Endometrium / pathology
Estrogen Receptor beta / genetics
Estrogen Receptor beta / metabolism*
Female
Humans
Stromal Cells / metabolism

Substances

CD47 Antigen
CD47 protein, human
ESR2 protein, human
Estrogen Receptor beta