NFAT5 contributes to osmolality-induced MCP-1 expression in mesothelial cells.
NFAT5 contributes to osmolality-induced MCP-1 expression in mesothelial cells.
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DOI：
10.1155/2012/513015
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发表时间：
2012
影响因子：
4.6
通讯作者：
Neuhofer W
中科院分区：
文献类型：
--
作者：
Küper C;Beck FX;Neuhofer W
C-C趋化因子单核细胞趋化蛋白-1（MCP-1）在高葡萄糖浓度和/或高渗透压下的间皮细胞中的表达增加在持续非卧床腹膜透析（CAPD）期间腹膜纤维化的发展中起着至关重要的作用。最近的研究表明，在肾细胞中，渗透压诱导的MCP-1上调是由细胞因子敏感性转录因子，活化T细胞核因子5（NFAT 5）介导的。本研究解决了这样一个问题，即高渗透压是否会激活PD液中的NFAT 5，从而促进间皮细胞系Met 5A中MCP-1的表达。通过向生长培养基中添加葡萄糖、NaCl或甘露醇诱导的高渗透压增加了NFAT 5活性并刺激了Met 5A细胞中MCP-1的表达。siRNA介导的NFAT 5敲低显著减弱了渗透压诱导的MCP-1上调。高渗还可诱导核因子-κB（NF-κB）活化。因此，药物抑制NF-κB可显著降低渗透压诱导的MCP-1表达。总之，这些结果表明，高渗透压激活转录因子NFAT 5在间皮细胞。NFAT 5反过来上调MCP-1，可能与NF-κB结合，因此可能参与CAPD期间腹膜纤维化的发展。
Increased expression of the C-C chemokine monocyte chemoattractant protein-1 (MCP-1) in mesothelial cells in response to high glucose concentrations and/or high osmolality plays a crucial role in the development of peritoneal fibrosis during continuous ambulatory peritoneal dialysis (CAPD). Recent studies suggest that in kidney cells osmolality-induced MCP-1 upregulation is mediated by the osmosensitive transcription factor, nuclear factor of activated T cells 5 (NFAT5). The present study addressed the question of whether activation of NFAT5 by hyperosmolality, as present in PD fluids, contributes to MCP-1 expression in the mesothelial cell line Met5A. Hyperosmolality, induced by addition of glucose, NaCl, or mannitol to the growth medium, increased NFAT5 activity and stimulated MCP-1 expression in Met5A cells. siRNA-mediated knockdown of NFAT5 attenuated osmolality-induced MCP-1 upregulation substantially. Hyperosmolality also induced activation of nuclear factor-κB (NF-κB). Accordingly, pharmacological inhibition of NF-κB significantly decreased osmolality-induced MCP-1 expression. Taken together, these results indicate that high osmolalities activate the transcription factor NFAT5 in mesothelial cells. NFAT5 in turn upregulates MCP-1, likely in combination with NF-κB, and thus may participate in the development of peritoneal fibrosis during CAPD.
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