SFRP1 suppresses granulosa cell proliferation and migration through inhibiting JNK pathway

¹ Department of Endocrinology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, 315010 Ningbo, Zhejiang, China

² Department of Gynecology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, 315010 Ningbo, Zhejiang, China

³ Department of Global Health, Ningbo Institute of Life and Health Industry, Hwa Mei Hospital, University of Chinese Academy of Sciences, 315010 Ningbo, Zhejiang, China

^*Correspondence: liangxia667@163.com (Liang Xia)

Clin. Exp. Obstet. Gynecol. 2021, 48(5), 1193–1199; https://doi.org/10.31083/j.ceog4805190

Submitted: 6 April 2021 | Revised: 21 May 2021 | Accepted: 15 June 2021 | Published: 15 October 2021

This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

Abstract

Background: Secreted frizzled-related protein 1 (SFRP1) functions as a Wnt antagonist to repress the proliferation and migration of epithelial ovarian cancer cells. Recent research has shown that SFRP1 was reduced in the subcutaneous abdominal adipose stem cells isolated from patients with polycystic ovarian syndrome (PCOS). Regardless, the regulatory role and mechanism of SFRP1 in the proliferation and migration of granulosa cells during development of PCOS are scarce. Methods: SFRP1 expression was analyzed in plasma samples from patients with PCOS or immortalized human granulosa cells (KGN). Cell counting kit-8 (CCK-8) and colony formation assays were used to analyze the cell viability and proliferation of KGN, respectively. Cell apoptosis was analyzed by flow cytometry, and migration was detected by transwell. Results: SFRP1 expression was lower in plasma samples isolated from patients with PCOS than the healthy control. Immortalized human granulosa cells (KGN) also showed decreased SFRP1 expression compared to normal ovarian epithelial IOSE80 cells. pcDNA-mediated over-expression of SFRP1 reduced the cell viability and proliferation of KGN via cell counting kit-8 (CCK-8) and colony formation assays, respectively. Flow cytometry, analysis showed that the cell apoptosis of KGN was promoted by SFRP1. Ectopic expression of SFRP1 retarded cell migration with down-regulation of MMP2, MMP9, and vimentin. JNK phosphorylation was reduced in KGN with SFRP1 over-expression. Conclusion: SFRP1 contributed to the suppression of granulosa cell proliferation and migration through inhibition of JNK activation, providing a promising molecular target for PCOS.

Keywords

SFRP1

Granulosa cell

Proliferation

Migration

JNK

Polycystic ovarian syndrome

Funding

2019HMKY32/Hwa Mei Research Fund of Hwa Mei Research Fund of Hwa Mei Hospital, University of Chinese Academy of Sciences

Figures

Fig. 1.

Previous article in this issue

Next article in this issue

Fig. 1.

Downregulation of SFRP1 in patients with PCOS.(A) SFRP1 was downregulated in the plasma samples from PCOS patients compared to qualified non-PCOS patients (healthy controls) by qRT-PCR. (B) The mRNA expression of SFRP1 was downregulated in KGN cells compared to that in IOSE80 cells by qRT-PCR. (C) The protein expression of SFRP1 was downregulated in KGN cells compared to that in IOSE80 cells by western blot. ** p $<$ 0.01 vs. healthy controls or IOSE80 group.

1 of 5

Clin. Exp. Obstet. Gynecol. Print ISSN 0390-6663 Electronic ISSN 2709-0094