Tie1 contributes to the development of ovarian hyperstimulation syndrome under the regulation of EGR1 in granulosa cells

Sun Lihua; Tian Hui; Xue Songguo; Ye Hongjuan; Xue Xue; Wang Rongxiang; Liu Yu; Zhang Caixia; Chen Qiuju; Gao Shaorong

doi:10.1038/s12276-021-00722-8

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자료유형: 학술저널

저자정보: Sun Lihua (Tongji University) Tian Hui (Tongji University School of Medicine) Xue Songguo (Tongji University School of Medicine) Ye Hongjuan (Tongji University School of Medicine) Xue Xue (Tongji University School of Medicine) Wang Rongxiang (Tongji University School of Medicine) Liu Yu (Tongji University School of Medicine) Zhang Caixia (Tongji University School of Medicine) Chen Qiuju (Shanghai JiaoTong University School of Medicine) Gao Shaorong (Tongji University)

저널정보: 대한생화학·분자생물학회 Experimental and Molecular Medicine Experimental and Molecular Medicine 제54권

발행연도: 2022.1

수록면: 1 - 10 (10page)

DOI: 10.1038/s12276-021-00722-8

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The expression of tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 (Tie1), a transmembrane protein expressed almost exclusively by endothelial cells, has been reported in granulosa cells. However, its significance in ovarian hyperstimulation syndrome (OHSS), which can occur after the injection of gonadotropins in infertile women undergoing controlled ovarian stimulation, is unknown. Here, we report significantly increased Tie1 and vascular endothelial growth factor (VEGF) expression in cultured granulosa cells from OHSS patients, as well as ovaries from rats with experimentally established OHSS, compared to controls, with the levels of both proteins also increasing in granulosa and SVOG cells (a nontumorigenic human granulosa-lutein cell line) treated with an acute dose of human chorionic gonadotropin (hCG). Tie1 silencing abolished the hCG-induced VEGF level in SVOG cells and attenuated the progression of OHSS in rats, as determined by histological analysis. Further studies in SVOG cells revealed that the hCG-induced upregulation of Tie1 expression involved the phosphoinositide 3-kinase/protein kinase B signaling pathway. We also report that early growth response protein 1 (EGR1), whose expression was also upregulated by hCG, bound directly to the Tie1 promoter and activated its transcription. Taken together, our results indicate that Tie1 may be a therapeutic target in cases of moderate-to-severe OHSS. Further studies are needed to address its clinical relevance.

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Sun Lihua

소속기관 Tongji University

주요연구분야 자연과학 > 화학

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Tian Hui