IMPLICATION OF ANGIOGENIC FACTORS IN FEMALE REPRODUCTIVE TRACT

血管生成因子对女性生殖道的影响

• 批准号: 14207064
• 负责人: TAKETANI Yuji
• 金额: $ 33.95万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14207064/
• 关键词: adiponectin; endometrium; endometriosis; implantation; receptor; AMPkinase; ミッドカイン; 子宮内膜症; GnRHアナログ; BrdU取り込み; 腹腔内貯留液; 卵胞液; 血管新生; 妊娠中毒症; sVEGFR-1(sFlt-1); IP-10; 血管新生抑制薬; マウス子宮内膜症モデル

Adiponectin, a pleiotropic cytokine, exerts its effects via the specific receptors, Adipo R1 and Adipo R2. Whereas circulating adiponectin concentrations decrease in women with endometriosis and endometrial cancer, possible effects of adiponectin and the presence of the receptors in the endometrium have not been determined. In this study, we examined the expression of adiponectin receptors, Adipo R1 and Adipo R2 in the human endometrium, and assessed effects of adiponectin in the endometrial cells. Expression of Adipo R1 and Adipo R2 in the endometrial tissues was evaluated by real-time quantitative PCR, in situ hybridization, and Western blotting. The effects of adiponectin on phosphorylation of AMP-activate protein kinase (AMPK), a regulator of energy homeostasis, in cultured endometrial stromal cells (ESCs) and epithelial cells (EECs) were studied by Western blotting. The effects of adiponectin on IL-1b-induced secretion of IL-6,IL-8 and MCP-1 from cultured ESCs were determined using specific ELISAs. The expression of Adipo R1 and Adipo R2 was detected in the endometrium. The expression of both genes was increased in the mid-luteal phase, the period of embryo implantation. In situ hybridization revealed that both Adipo R1 and Adipo R2 appeared to be equally expressed in the epithelial cells and in the stromal cells. Adiponectin increased phosphorylation of AMPK in ESCs and EECs. Adiponectin decreased IL-1b-induced secretion of IL-6,IL-8 and MCP-1 from ESCs. These findings suggest that adiponectin exerts energy-homeostatic and anti-inflammatory effects in the endometrium, and these effects might be relevant to pathological and physiological endometrium-related events such as implantation and endometriosis.

脂联素是一种多效细胞因子，通过特定受体 Adipo R1 和 Adipo R2 发挥作用。尽管患有子宫内膜异位症和子宫内膜癌的女性循环脂联素浓度降低，但脂联素可能产生的影响以及子宫内膜中受体的存在尚未确定。在本研究中，我们检测了人子宫内膜中脂联素受体 Adipo R1 和 Adipo R2 的表达，并评估了脂联素对子宫内膜细胞的影响。通过实时定量PCR、原位杂交和Western blotting评估子宫内膜组织中Adipo R1和Adipo R2的表达。通过蛋白质印迹法研究了脂联素对培养的子宫内膜基质细胞 (ESC) 和上皮细胞 (EEC) 中能量稳态调节剂 AMP 激活蛋白激酶 (AMPK) 磷酸化的影响。使用特异性 ELISA 测定脂联素对 IL-1b 诱导的培养 ESC 分泌 IL-6、IL-8 和 MCP-1 的影响。子宫内膜中检测到Adipo R1和Adipo R2的表达。这两个基因的表达在黄体中期（胚胎着床期）中增加。原位杂交显示，Adipo R1 和 Adipo R2 在上皮细胞和基质细胞中似乎同等表达。脂联素增加 ESC 和 EEC 中 AMPK 的磷酸化。脂联素减少 IL-1b 诱导的 ESC 分泌 IL-6、IL-8 和 MCP-1。这些发现表明脂联素在子宫内膜中发挥能量稳态和抗炎作用，这些作用可能与子宫内膜病理和生理相关事件（如着床和子宫内膜异位症）有关。

项目成果

Serum adiponectin concentrations are decreased in women with endometriosis

• DOI: 10.1093/humrep/dei233
• 发表时间: 2005-12-01
• 期刊: HUMAN REPRODUCTION
• 影响因子: 6.1
• 作者: Takemura, Y;Osuga, Y;Taketani, Y
• 通讯作者: Taketani, Y

GnRH II as a possible cytostatic regulator in the development of endometriosis

• DOI: 10.1093/humrep/dei192
• 发表时间: 2005-11-01
• 期刊: HUMAN REPRODUCTION
• 影响因子: 6.1
• 作者: Morimoto, C;Osuga, Y;Taketani, Y
• 通讯作者: Taketani, Y

Yoshino O, Osuga Y, Koga K, Hirota Y, Yano T, Tsutsumi O, et al.: "Upregulation of interleukin-8 by hypoxia in human ovaries"Am J Reprod Immunol. 50・4. 286-290 (2003)

Yoshino O、Osuga Y、Koga K、Hirota Y、Yano T、Ttsutsumi O 等：“人卵巢缺氧导致白细胞介素 8 的上调”Am J Reprod Nutrition 50・4 (2003)。

Evidence for the presence of protease-activated receptor 2 (PAR2) and its possible implication in remodeling of human endometrium

蛋白酶激活受体 2 (PAR2) 存在的证据及其在人类子宫内膜重塑中的可能意义

• 发表时间: 2005
• 期刊: J Clin Endocrinol Metab (In press)
• 作者: Hirota Y;Osuga Y;Hirata T;Koga K;Yoshino O;Harada M;Morimoto C;Nose E.;Yano T.;Tsutsumi O.;Taketani Y
• 通讯作者: Taketani Y

Hirota Y, Osuga Y, Yoshino O, Koga K, Yano T, Hirata T, et al.: "Possible roles of thrombin-induced activation of protease-activated receptor 1 in human luteinized granulosa cells"J Clin Endocrinol Metab. 88・8. 3952-3957 (2003)

Hirota Y、Osuga Y、Yoshino O、Koga K、Yano T、Hirata T 等：“人黄素化颗粒细胞中凝血酶诱导的蛋白酶激活受体 1 激活的可能作用”J Clin Endocrinol Metab 88・8。 .3952-3957 (2003)