Endometrial stromal cell ferroptosis promotes angiogenesis in endometriosis.
Endometrial stromal cell ferroptosis promotes angiogenesis in endometriosis.
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DOI：
10.1038/s41420-022-00821-z
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发表时间：
2022-01-17
影响因子：
7
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Li G;Lin Y;Zhang Y;Gu N;Yang B;Shan S;Liu N;Ouyang J;Yang Y;Sun F;Xu H
子宫内膜异位症是一种慢性疾病，其特征是子宫外存在子宫样组织，与病变中的铁过载和氧化应激有关。虽然铁超载可以触发铁凋亡，但以前关于铁凋亡抵抗和铁凋亡在增生性病变中的研究结果是矛盾的。在这里，我们发现一些与囊液接触的囊壁间质细胞发生了铁下垂。令人惊讶的是，子宫内膜间质细胞铁凋亡引发了血管生成，炎症和生长细胞因子的产生。特别是，血管生成细胞因子，如血管内皮生长因子A（VEGFA）和白细胞介素8（IL 8），促进体外人脐静脉内皮细胞（HUVEC）血管形成。此外，我们发现，抑制p38丝裂原活化蛋白激酶/信号转导和转录激活因子6（p38 MAPK/STAT 6）信号转导抑制VEGFA和IL 8的表达时，子宫内膜间质细胞发生ferroptosis。值得注意的是，VEGFA和IL 8显示出局部表达，并且与来自子宫内膜异位症患者的对照和在位子宫内膜样品相比，在异位病变中显著上调。因此，我们的研究表明，子宫内膜间质细胞铁凋亡在卵巢腺瘤可能会触发细胞因子分泌，并通过旁分泌作用促进邻近病变的血管生成，从而推动子宫内膜异位症的发展，为临床实践和开发治疗子宫内膜异位症的药物提供了理论基础。
Endometriosis, a chronic disorder characterised by the presence of endometrial-like tissue outside the uterus, is associated with iron overload and oxidative stress in the lesion. Although it is well established that iron overload can trigger ferroptosis, the results of previous studies on ferroptosis resistance and ferroptosis in endometriotic lesions are paradoxical. Here, we found that some stromal cells of the cyst walls that were in contact with the cyst fluid underwent ferroptosis. Surprisingly, endometrial stromal cell ferroptosis triggered the production of angiogenic, inflammatory and growth cytokines. In particular, angiogenic cytokines, such as vascular endothelial growth factor A (VEGFA) and interleukin 8 (IL8), promoted human umbilical vein endothelial cell (HUVEC) vascular formation in vitro. Moreover, we found that inhibition of p38 mitogen-activated protein kinase/signal transducer and activator of transcription 6 (p38 MAPK/STAT6) signalling represses VEGFA and IL8 expression when endometrial stromal cells undergo ferroptosis. Notably, VEGFA and IL8 showed localised expression and were significantly upregulated in ectopic lesions compared to control and eutopic endometrium samples from patients with endometriosis. Thus, our study reveals that endometrial stromal cell ferroptosis in the ovarian endometrioma may trigger cytokine secretion and promote angiogenesis of adjacent lesions via paracrine actions to drive the development of endometriosis, providing a rationale for translation into clinical practice and developing drugs for endometriosis.
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影响因子：
64.5
作者：
Han SJ;Jung SY;Wu SP;Hawkins SM;Park MJ;Kyo S;Qin J;Lydon JP;Tsai SY;Tsai MJ;DeMayo FJ;O'Malley BW
通讯作者：
O'Malley BW
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
11.2
作者：
Karuppagounder SS;Alin L;Chen Y;Brand D;Bourassa MW;Dietrich K;Wilkinson CM;Nadeau CA;Kumar A;Perry S;Pinto JT;Darley-Usmar V;Sanchez S;Milne GL;Pratico D;Holman TR;Carmichael ST;Coppola G;Colbourne F;Ratan RR
通讯作者：
Ratan RR
铁转运蛋白依赖性铁稳态可防止氧化应激诱导的髓核细胞铁死亡并改善体内椎间盘退变
影响因子：
--
作者：
Lu S;Song Y;Luo R;Li S;Li G;Wang K;Liao Z;Wang B;Ke W;Xiang Q;Chen C;Wu X;Zhang Y;Ling L;Yang C
通讯作者：
Yang C
DOI：
10.1073/pnas.1415518111
发表时间：
2014-11-25
影响因子：
11.1
作者：
Linkermann, Andreas;Skouta, Rachid;Krautwald, Stefan
通讯作者：
Krautwald, Stefan