Expression and regulation of a novel identified TNFAIP8 family is associated with diabetic nephropathy
Expression and regulation of a novel identified TNFAIP8 family is associated with diabetic nephropathy
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一个新发现的 TNFAIP8 家族的表达和调节与糖尿病肾病相关。
DOI：
10.1016/j.bbadis.2010.08.003
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发表时间：
2010-11-01
影响因子：
6.2
通讯作者：
Yi, Fan
中科院分区：
文献类型：
--
作者：
Zhang, Shuya;Zhang, Yan;Yi, Fan
肿瘤坏死因子-α-诱导蛋白8（TNFAIP 8）家族是最近发现的具有相当大序列同源性的调节细胞和免疫稳态的蛋白质。然而，TNFAIP 8家族是否在肾脏中表达并有助于调节肾功能尚不清楚。因此，本研究旨在研究TNFAIP 8家族成员在肾脏中的表达，并探讨其在糖尿病肾病发生和发展中的可能作用。通过RT-PCR和Western blot分析，我们发现TNFAIP 8家族的所有成员都在肾脏中被检测到。TNFAIP 8和TIPE 2的表达在链脲佐菌素（STZ）诱导的糖尿病大鼠的肾小球中显著增加，并且这种上调在糖尿病患者的肾活检中得到进一步证实。在体外研究中，TNFAIP 8在肾小球系膜细胞而不是足细胞中响应于高葡萄糖而上调。TNFAIP 8的表达与系膜细胞增殖直接相关，这种调节与NADPH氧化酶介导的信号通路有关。然而，我们未能观察到高葡萄糖对系膜细胞和足细胞中TIPE 2的上调。本研究阐明了TNFAIP 8家族在糖尿病肾病中的作用。这些发现首次证明TNFAIP 8是连接系膜细胞增殖和糖尿病肾损伤的信号转导途径的关键组分之一（C）。2010 Elsevier B V.保留所有权利
Tumor necrosis factor-alpha-inducible protein 8 (TNFAIP8) family are very recently identified proteins which share considerable sequence homology to regulate cellular and immune homeostasis. However, it is unknown whether TNFAIP8 family is expressed in the kidney and contributes to the regulation of renal functions. Therefore, the present study was designed to characterize the members of TNFAIP8 family in the kidney and to explore their possible roles in the development and progression of diabetic nephropathy. By RT-PCR and Western blot analyses, we found that all members of TNFAIP8 family were detected in the kidney. TNFAIP8 and TIPE2 expression was significantly increased in glomeruli from streptozotocin (STZ)induced diabetic rats, and this upregulation was further confirmed in renal biopsies of diabetic patients. In in vitro study, TNFAIP8 was upregulated in response to high glucose in mesangial cells rather than podocytes. Moreover, a direct correlation was observed between expression of TNFAIP8 and mesangial cell proliferation and this regulation was associated with NADPH oxidase-mediated signaling pathway. However, we failed to observe the upregulation of TIPE2 in both mesangial cells and podocytes in response to high glucose In conclusion, the present study addressed the role of TNFAIP8 family in diabetic nephropathy These findings for the first time demonstrate that TNFAIP8 is one of critical components of a signal transduction pathway that links mesangial cell proliferation to diabetic renal injury (C) 2010 Elsevier B V. All rights reserved