Thalidomide Suppresses Angiogenesis Through the Signal Transducer and Activator of Transcription 3/SP4 Signaling Pathway in the Peritoneal Membrane.
Thalidomide Suppresses Angiogenesis Through the Signal Transducer and Activator of Transcription 3/SP4 Signaling Pathway in the Peritoneal Membrane.
复制标题
沙利度胺通过腹膜中转录 3/SP4 信号通路的信号转导器和激活剂抑制血管生成
DOI：
10.3389/fphys.2021.712147
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发表时间：
2021
影响因子：
4
通讯作者：
Yuan W
中科院分区：
文献类型：
--
作者：
Zhu N;Wang L;Guo H;Jia J;Gu L;Wang X;Yang M;Guan H;Yuan W
腹膜血管生成是限制尿毒症患者腹膜透析（PD）期间腹膜超滤的关键病理生理因素。沙利度胺已被证实通过抑制血管内皮生长因子（VEGF）的分泌来抑制血管生成，但沙利度胺在PD过程中抑制血管增殖的确切机制仍不清楚。本研究的目的是探讨沙利度胺是否可以控制人腹膜间皮细胞 (HPMC) 产生 VEGF 的减少。用 IL-6 与可溶性 IL-6 受体 (sIL-6R) 联合刺激 HPMC 可促进 VEGF 表达和分泌，但沙利度胺治疗通过涉及信号转导子和转录激活子 3 (STAT3) 和 SP4 的转录机制减弱了这些作用。用沙利度胺培养的 HPMC 的条件培养基抑制血管生成内皮管的形成，这可以通过沉默 SP4 来进一步阻断，并通过过表达 SP4 来促进。在体内，用沙利度胺腹膜内治疗的假手术大鼠、假手术+PD大鼠、5/6肾切除（5/6Nx）大鼠、5/6Nx+PD大鼠和5/6Nx+PD大鼠腹膜血管生成的诱导表明，沙利度胺参与控制几个关键的内皮特异性靶标，包括VEGFR2、VEGFR3、SP4和STAT3表达和新血管形成，证实了沙利度胺和 STAT3/SP4 信号传导在这些过程中的作用。总而言之，这些发现确定了一种将沙利度胺、STAT3/SP4 信号传导和腹膜血管生成联系起来的新机制。
Peritoneal angiogenesis is the key pathophysiological factor that limits peritoneal ultrafiltration during peritoneal dialysis (PD) in uremic patients. Thalidomide has been confirmed to inhibit angiogenesis by inhibiting the secretion of vascular endothelial growth factor (VEGF), but the exact mechanism by which thalidomide inhibits vascular proliferation during PD is still unclear. Here, the objective of the present study was to investigate whether the reduction in VEGF production by human peritoneal mesothelial cells (HPMCs) was controlled by thalidomide. Stimulation of HPMCs with IL-6 in combination with soluble IL-6 receptor (sIL-6R) promoted VEGF expression and secretion, but these effects were attenuated by thalidomide treatment through a transcriptional mechanism that involved signal transducer and activator of transcription 3 (STAT3) and SP4. Conditioned medium from HPMCs cultured with thalidomide inhibited angiogenic endothelial tube formation, which could be further blocked by silencing SP4 and promoted by overexpressing SP4. In vivo, induction of peritoneal angiogenesis in sham rats, sham+PD rats, 5/6 nephrectomy (5/6Nx) rats, 5/6Nx+PD rats, and 5/6Nx+PD rats intraperitoneally treated with thalidomide showed that thalidomide was involved in the control of several key endothelial–specific targets, including VEGFR2, VEGFR3, SP4, and STAT3 expression and new vessel formation, confirming the role of thalidomide and STAT3/SP4 signaling in these processes. Taken together, these findings identify a novel mechanism that links thalidomide, STAT3/SP4 signaling, and angiogenesis in the peritoneal membrane.
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DOI：
10.1093/ndtplus/sfn127
发表时间：
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期刊：
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影响因子：
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影响因子：
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DOI：
10.1186/1756-9966-27-60
发表时间：
2008-11-04
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
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