FLI1 and ERG protein degradation is regulated via Cathepsin B lysosomal pathway in human dermal microvascular endothelial cells.
FLI1 and ERG protein degradation is regulated via Cathepsin B lysosomal pathway in human dermal microvascular endothelial cells.
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DOI：
10.1111/micc.12660
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Trojanowska M
中科院分区：
文献类型：
--
作者：
Mazzotta C;Marden G;Farina A;Bujor A;Trojanowski MA;Trojanowska M
在硬皮病患者的微血管内皮细胞中，Friend白血病整合1和红细胞转化特异性是重要的内皮细胞稳态调节因子，它们的缺失参与了疾病的发病机制。这项研究的目的是确定在微血管内皮细胞中涉及Friend白血病整合1和红细胞转化特异性蛋白周转的机制。用Western blotting和毛细血管形态发生学方法评价溶酶体和蛋白酶体抑制剂对Friend白血病整合1和红细胞转化特异性水平的影响。检测硬皮病和对照血清对Friend白血病整合1和红细胞转化特异性水平的影响。干扰素α或Poly：(IC)对Friend白血病整合1和红细胞转化特异性蛋白水平的降低可通过阻断溶酶体(亮胃素和组织蛋白酶B抑制剂)或蛋白体降解(MG132)而逆转。MG132、亮肽素或CTSB-(I)也可拮抗Poly：(IC)或干扰素α的抗血管生成作用。与对照血清相比，硬皮病血清降低了Friend白血病整合1和红细胞转化特异性的蛋白水平。在大多数血清处理的样本中，CTSB(I)治疗增加了Friend白血病整合1和红细胞转化特异性水平。抑制组织蛋白酶B能有效逆转干扰素α或硬皮病血清治疗后Friend白血病整合蛋白1和红细胞转化特异性蛋白水平的降低，提示靶向组织蛋白酶B可能在SSc血管疾病中具有有益的作用。
Friend leukemia integration 1 and erythroblast transformation‐specific, important regulators of endothelial cell homeostasis, are reduced in microvascular endothelial cells in scleroderma patients, and their deficiency has been implicated in disease pathogenesis. The goal of this study was to identify the mechanisms involved in the protein turnover of friend leukemia integration 1 and erythroblast transformation‐specific in microvascular endothelial cells. The effects of lysosome and proteosome inhibitors on friend leukemia integration 1 and erythroblast transformation‐specific levels were assessed by Western blotting and capillary morphogenesis. The effect of scleroderma and control sera on the levels of friend leukemia integration 1 and erythroblast transformation‐specific was examined. The reduction in the protein levels of friend leukemia integration 1 and erythroblast transformation‐specific in response to interferon α or Poly:(IC) was reversed by blocking either lysosomal (leupeptin and Cathepsin B inhibitor) or proteosomal degradation (MG132). MG132, leupeptin or CTSB‐(i) also counteracted the anti‐angiogenic effects of Poly:(IC) or interferon α. Scleroderma sera reduced protein levels of friend leukemia integration 1 and erythroblast transformation‐specific in comparison to control sera. Treatment with CTSB(i) increased the levels of friend leukemia integration 1 and erythroblast transformation‐specific in a majority of serum‐treated samples. Inhibition of cathepsin B was effective in reversing the reduction of friend leukemia integration 1 and erythroblast transformation‐specific protein levels after treatment with interferon α or scleroderma sera, suggesting that targeting cathepsin B may have a beneficial effect in SSc vascular disease.
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影响因子：
4.5
作者：
Nagai N;Ohguchi H;Nakaki R;Matsumura Y;Kanki Y;Sakai J;Aburatani H;Minami T
通讯作者：
Minami T
影响因子：
4.6
作者：
Asano Y;Bujor AM;Trojanowska M
通讯作者：
Trojanowska M
影响因子：
6
作者：
Kubo, M;Czuwara-Ladykowska, J;Trojanowska, M
通讯作者：
Trojanowska, M
影响因子：
12.8
作者：
Chouri, Eleni;Servaas, Nila H.;Radstake, Timothy R. D. J.
通讯作者：
Radstake, Timothy R. D. J.
DOI：
10.1165/rcmb.2016-0200oc
发表时间：
2017-07-01
影响因子：
6.4
作者：
Looney, Agnieszka P.;Han, Rong;Trojanowska, Maria
通讯作者：
Trojanowska, Maria