Complement-mediated glomerular injury is reduced by inhibition of protein-tyrosine phosphatase 1B.
Complement-mediated glomerular injury is reduced by inhibition of protein-tyrosine phosphatase 1B.
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抑制蛋白酪氨酸磷酸酶 1B 可减少补体介导的肾小球损伤。
DOI：
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
A. Cybulsky
中科院分区：
文献类型：
--
作者：
Lisa Nezvitsky;M. Tremblay;T. Takano;J. Papillon;A. Cybulsky
未折叠蛋白反应和内质网相关降解（ERAD）有助于肾小球疾病中的损伤，包括补体C5 b-9介导的损伤。在本研究中，我们解决蛋白酪氨酸磷酸酶1B（PTP 1B）在补体介导的肾小球损伤和ERAD中的作用。在暴露于补体的肾小球上皮细胞（GECs）/足细胞和PTP 1B缺陷小鼠胚胎成纤维细胞中，PTP 1B的抑制/缺失降低了ERAD，如ERAD报告分子CD 3 δ所监测。在经过补体处理的GEC中，PTP 1B的过表达对ERAD产生了与PTP 1B缺乏类似的作用。补体介导的细胞毒性在PTP 1B过表达后降低，并且在PTP 1B抑制后趋于降低。PTP 1B通过未折叠蛋白反应的肌醇需要-1 α分支增强某些ERAD组分的诱导。与野生型同窝小鼠相比，患有抗肾小球基底膜肾炎的PTP 1B基因敲除小鼠的蛋白尿减少，足细胞丢失和内质网功能障碍减少。这些结果表明，PTP 1B的内源性水平受到严格调控，过表达和抑制都可以影响ERAD。PTP 1B缺失在培养细胞和抗肾小球基底膜肾炎中的细胞保护作用表明，PTP 1B可能是补体介导的疾病的治疗靶点。
The unfolded protein response and endoplasmic reticulum-associated degradation (ERAD) contribute to injury in renal glomerular diseases, including those mediated by complement C5b-9. In the present study, we address the role of protein-tyrosine phosphatase 1B (PTP1B) in complement-mediated glomerular injury and ERAD. In glomerular epithelial cells (GECs)/podocytes and PTP1B-deficient mouse embryonic fibroblasts exposed to complement, inhibition/deletion of PTP1B reduced ERAD, as monitored by the ERAD reporter CD3δ. Overexpression of PTP1B produced an effect similar to PTP1B deficiency on ERAD in complement-treated GECs. Complement-mediated cytotoxicity was reduced after PTP1B overexpression and tended to be reduced after PTP1B inhibition. PTP1B enhanced the induction of certain ERAD components via the inositol-requiring-1α branch of the unfolded protein response. PTP1B knockout mice with anti-glomerular basement membrane glomerulonephritis had decreased proteinuria and showed less podocyte loss and endoplasmic reticulum dysfunction compared with wild-type littermates. These results imply that endogenous levels of PTP1B are tightly regulated and that both overexpression and inhibition can affect ERAD. The cytoprotective effects of PTP1B deletion in cultured cells and in anti-glomerular basement membrane nephritis suggest that PTP1B may potentially be a therapeutic target in complement-mediated diseases.
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影响因子：
33.6
作者：
Guerriero CJ;Brodsky JL
通讯作者：
Brodsky JL
人HRD1启动子具有功能性展开的蛋白质反应元件，XBP1而非ATF6直接结合。
影响因子：
2.7
作者：
Yamamoto K;Suzuki N;Wada T;Okada T;Yoshida H;Kaufman RJ;Mori K
通讯作者：
Mori K
DOI：
10.1042/bj20110373
发表时间：
2011-09-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Agouni A;Mody N;Owen C;Czopek A;Zimmer D;Bentires-Alj M;Bence KK;Delibegović M
通讯作者：
Delibegović M
影响因子：
13.8
作者：
Yip, Shu-Chin;Saha, Sayanti;Chernoff, Jonathan
通讯作者：
Chernoff, Jonathan
影响因子：
7.5
作者：
Brodsky, Jeffrey L.;Skach, William R.
通讯作者：
Skach, William R.