Suppressors of cytokine signaling (SOCS) family is constituted by cytokine-inducible proteins that modulate receptor signal transduction via tyrosine kinases, mainly the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway. Differential SOCS expression was noted in renal cells that were incubated with inflammatory stimuli, but the role of SOCS in the pathogenesis of renal diseases is not yet well defined. Because angiotensin II (Ang II) plays a key role in renal disease, SOCS proteins were studied as a novel mechanism involved in the negative regulation of Ang II-mediated processes. Systemic Ang II infusion for 3 d increased the renal mRNA expression of SOCS-3 and SOCS-1. SOCS protein synthesis was found in glomerular mesangial area and tubules. In cultured mesangial cells and tubular epithelial cells, Ang II induced a rapid and transient SOCS-3 and SOCS-1 expression in parallel with JAK2 and STAT1 activation. In both cell types, overexpression of SOCS proteins prevented the STAT activation in response to Ang II. SOCS expression observed in Ang II-infused rats and in Ang II-stimulated cells was significantly inhibited by treatment with AT(1) but not AT(2) receptor antagonist and was attenuated in mesangial cells from AT(1a)-deficient mice, demonstrating the implication of AT(1) in those responses. In SOCS-3 knockdown studies, antisense oligonucleotides inhibited the expression of SOCS-3 and increased the Ang II-induced STAT activation and c-Fos/c-Jun expression, then resulting in a more severe renal damage. These results suggest that SOCS proteins may act as negative regulators of Ang II signaling in renal cells and implicate SOCS as important modulators of renal damage.

译文

细胞因子信号传导抑制子 (SOCS) 家族由细胞因子诱导蛋白组成,这些蛋白通过酪氨酸激酶调节受体信号转导,主要是Janus激酶信号转导和转录激活子 (JAK-STAT) 途径。在与炎症刺激一起孵育的肾细胞中发现了不同的SOCS表达,但是SOCS在肾脏疾病发病机理中的作用尚未明确。由于血管紧张素II (Ang II) 在肾脏疾病中起关键作用,因此研究了SOCS蛋白作为参与Ang II介导过程负调节的新机制。全身Ang II输注3 d可增加SOCS-3和SOCS-1的肾脏mRNA表达。在肾小球系膜区和肾小管中发现了SOCS蛋白合成。在培养的系膜细胞和肾小管上皮细胞中,Ang II与JAK2和STAT1激活平行地诱导快速且短暂的SOCS-3和SOCS-1表达。在两种细胞类型中,SOCS蛋白的过表达均阻止了响应Ang II的STAT激活。在注入Ang II的大鼠和Ang II刺激的细胞中观察到的SOCS表达通过AT(1) 处理而显着抑制,但不抑制AT(2) 受体拮抗剂,并且在AT(1a) 缺陷小鼠的系膜细胞中减弱,证明AT(1) 在这些回应中的含义。在SOCS-3敲低研究中,反义寡核苷酸抑制SOCS-3的表达并增加Ang II诱导的STAT激活和c-Fos/c-6月表达,从而导致更严重的肾损伤。这些结果表明,SOCS蛋白可能充当肾细胞中Ang II信号传导的负调节剂,并暗示SOCS是肾损伤的重要调节剂。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录