Down-regulation of PBK inhibits proliferation of human endometrial stromal cells in thin endometrium

Reproductive Biology and Endocrinology

Yishan Dong¹  Limin Wang²  Qi Zhu²  Yali Hu³  Haining Lv⁴  Huiyan Wang⁴  Chenrui Cao⁴  Xiwen Zhang⁴  Simin Yao⁴  Zhenhua Zhou⁴  Peipei Jiang⁴  Wenjing Gou⁴  Dan Liu⁴  Chenyan Dai⁴  Guangfeng Zhao⁴ 

[1] Department of Obstetrics and Gynecology, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China;Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Graduate School of Peking Union Medical College, 321 Zhongshan Rd, 210008, Nanjing, China;Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Graduate School of Peking Union Medical College, 321 Zhongshan Rd, 210008, Nanjing, China;Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China;Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China;

关键词: Thin endometrium;    RNA-seq;    Transcriptome;    PBK;    TOPK;    HESCs;   

DOI  :  10.1186/s12958-022-00903-8

来源: Springer

【 摘 要 】

BackgroundThin endometrium (TE) is a challenging clinical issue in the reproductive medicine characterized by inadequate endometrial thickness, poor response to estrogen and no effective treatments currently. At present, the precise pathogenesis of thin endometria remains to be elucidated. We aimed to explore the related molecular mechanism of TE by comparing the transcriptome profiles of late-proliferative phase endometria between TE and matched controls.MethodsWe performed a bulk RNA-Seq (RNA-sequencing) of endometrial tissues in the late-proliferative phase in 7 TE and 7 matched controls for the first time. Differential gene expression analysis, gene ontology enrichment analysis and protein-protein interactions (PPIs) network analysis were performed. Immunohistochemistry was used for molecular expression and localization in endometria. Human endometrial stromal cells (HESCs) were isolated and cultured for verifying the functions of hub gene.ResultsIntegrative data mining of our RNA-seq data in endometria revealed that most genes related to cell division and cell cycle were significantly inhibited, while inflammation activation, immune response and reactive oxygen species associated genes were upregulated in TE. PBK was identified as a hub of PPIs network, and its expression level was decreased by 2.43-fold in endometria of TE patients, particularly reduced in the stromal cells, which was paralleled by the decreased expression of Ki67. In vitro experiments showed that the depletion of PBK reduced the proliferation of HESCs by 50% and increased the apoptosis of HESCs by 1 time, meanwhile PBK expression was inhibited by oxidative stress (reduced by 76.2%), hypoxia (reduced by 51.9%) and inflammatory factors (reduced by approximately 50%). These results suggested that the insufficient expression of PBK was involved in the poor endometrial thickness in TE.ConclusionsThe endometrial transcriptome in late-proliferative phase showed suppressed cell proliferation in women with thin endometria and decreased expression of PBK in human endometrial stromal cells (HESCs), to which inflammation and reactive oxygen species contributed.

【 授权许可】

CC BY