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.

脂联素是一种多效性细胞因子，通过特异性受体Adipo R1和Adipo R2发挥作用。虽然循环脂联素浓度降低妇女子宫内膜异位症和子宫内膜癌，可能的影响脂联素和存在的受体在子宫内膜尚未确定。在这项研究中，我们研究了脂联素受体Adipo R1和Adipo R2在人子宫内膜中的表达，并评估了脂联素在子宫内膜细胞中的作用。采用实时荧光定量PCR、原位杂交和Western blotting检测Adipo R1和Adipo R2在子宫内膜组织中的表达。采用Western blotting方法观察脂联素对体外培养的子宫内膜间质细胞（ESCs）和上皮细胞（EECs）能量平衡调节因子AMP激活蛋白激酶（AMPK）磷酸化的影响。采用特异性ELISA法检测脂联素对IL-1b诱导的ESCs分泌IL-6、IL-8和MCP-1的影响。Adipo R1和Adipo R2在子宫内膜中均有表达。在黄体中期，即胚胎着床期，这两个基因的表达都有所增加。原位杂交显示，Adipo R1和Adipo R2似乎在上皮细胞和基质细胞中表达相等。脂联素增加AMPK在ESCs和EECs中的磷酸化。脂联素抑制IL-1b诱导的ESCs分泌IL-6、IL-8和MCP-1。这些结果表明，脂联素在子宫内膜中发挥能量平衡和抗炎作用，这些作用可能与子宫内膜相关的病理和生理事件，如着床和子宫内膜异位症。

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

Mechanical stretch stimulates interleukin-8 production in endometrial stromal cells: Possible implications in endometrium-related events

• DOI: 10.1210/jc.2004-1089
• 发表时间: 2005-02-01
• 期刊: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
• 影响因子: 5.8
• 作者: Harada, M;Osuga, Y;Taketani, Y
• 通讯作者: Taketani, Y

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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