Estrogen-increased SGK1 Promotes Endometrial Stromal Cell Invasion in Adenomyosis by Regulating with LPAR2

Adenomyosis is an estrogen-dependent gynecological disorder. The abnormal migration and invasion of the eutopic endometrium is thought to be the primary role in the pathogenesis of adenomyosis. However, the exact underlying mechanism remains unclear. This study investigated involvement of serum and glucocorticoid-regulated kinase 1 (SGK1) in the pathogenesis of adenomyosis. The SGK1 expression level was higher in the eutopic endometrium of adenomyosis. Upregulation of SGK1 can promote the migration, invasion of human stromal endometrial cells (HESC). Through RNA sequencing and other technical methods, we found that SGK1 regulates the expression of the important downstream molecule Lysophosphatidic acid receptor 2 (LPAR2), and ultimately regulates the expression level of functional proteins such as matrix metalloproteinase 2 and matrix metalloproteinase 9, which are related to migration and invasion. Then, we found that 17β-estradiol (E2) upregulated the expression of SGK1 in endometrial cells in a dose-dependent manner. Furthermore, SGK1 shRNA significantly suppressed the migration and invasion induced by E2 in endometrial cells, as well as the related factors. Our study revealed the possible role of SGK1 in the migration and invasion in the development of adenomyosis. Similar content being viewed by others Data Availability Not applicable. Code availability Not applicable.

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We thank the patients for their participation. We thank our colleagues at the Department of Gynecology and Obstetrics for helping with sample collection. Funding This study was supported by funds from the National Natural Science Foundation of China (81901457, 81802552, 81971332), the Natural Science Foundation of Guangdong Province (2018A030313545), and the Science Technology Program of Guangdong Province (201904010004). Author information Authors and Affiliations Contributions Yingchen Wu was responsible for the interpretation of data, experiment and article drafting; Qingxue Zhang and Guangzheng Zhong contributed to conception and study design; Hao Wang; Yi Li and Guangzheng Zhong was mainly in charge of the data analysis; Yihua Liang and Yangzi Li took part in the acquisition of data. All authors read and approved the final manuscript. Corresponding authors Ethics declarations Ethics approval and consent to participate All procedures performed in this study were in accordance with the ethical standards of the Ethics Committee of The Sun Yat-Sen Memorial Hospital of China (SYSEC-KY-KS-2021–160). Written informed consent was obtained from individual or guardian participants. Consent for publication Not applicable. Conflict of interest The authors declare no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Wu, Y., Wang, H., Li, Y. et al. Estrogen-increased SGK1 Promotes Endometrial Stromal Cell Invasion in Adenomyosis by Regulating with LPAR2. Reprod. Sci. 29, 3026–3038 (2022). https://doi.org/10.1007/s43032-022-00990-3 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-022-00990-3