Increased TRPC6 expression is associated with tubular epithelial cell proliferation and inflammation in diabetic nephropathy
Increased TRPC6 expression is associated with tubular epithelial cell proliferation and inflammation in diabetic nephropathy
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DOI：
10.1016/j.molimm.2017.12.014
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发表时间：
2018-02-01
影响因子：
3.6
通讯作者：
Chu, Xiaojing
中科院分区：
文献类型：
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作者：
Fu, Yanqin;Wang, Chongxian;Chu, Xiaojing
虽然TRPC 6的表达在糖尿病肾病（DN）大鼠模型中显著升高，但其在人DN中的表达和作用尚不清楚。因此，我们探讨了TRPC 6在DN后肾小管上皮细胞损伤的病理生理学中的作用。HK-2细胞在高糖培养基中培养以诱导DN细胞模型。转染Ad-TRPC 6和TRP 6 siRNA以过表达和敲低TRPC 6。我们发现TRPC 6在DN组织和细胞中表达显著上调。TRPC 6 siRNA抑制高糖诱导的HK-2细胞增殖，促进细胞凋亡，而Ad-TRPC 6则表现出相反的作用。此外，Ad-TRPC 6显著促进IL-8和IL-6的释放。随后的实验表明，活化T细胞核因子（NFAT）的信号通路被Ad-TRPC 6激活，TRPC 6 siRNA失活。NFAT信号传导抑制剂FK-506可消除TRPC 6对HK-2细胞的作用。这些结果表明，TRPC 6在DN中上调，并且可以通过抑制肾小管上皮细胞中的NFAT信号通路来促进细胞增殖和炎症。
Although TRPC6 expression is shown to be significantly elevated in a rat model diabetic nephropathy (DN), its expression and role in human DN are unclear. We thus explored the role of TRPC6 in the pathophysiology of tubular epithelial cell injury following DN. HK-2 cells were cultured in a high-glucose medium to induce a DN cell model. Ad-TRPC6 and TRP6 siRNA were transfected to overexpress and knock down TRPC6. We found that TRPC6 expression was significantly upregulated in DN tissues and cells. TRPC6 siRNA inhibited cell proliferation and promoted cell apoptosis in HK-2 cells treated with high glucose, whereas Ad-TRPC6 showed the opposite effect. Furthermore, Ad-TRPC6 significantly promoted release of IL-8 and IL-6. Subsequent experiments demonstrated that the signaling pathway of nuclear factor of activated T cells (NFAT) was activated by Ad-TRPC6 and deactivated by TRPC6 siRNA. The NFAT signaling inhibitor, FK-506, eliminated the effect of TRPC6 on HK-2 cells. These results suggest that TRPC6 was upregulated in DN and could promote cell proliferation and inflammation by inhibiting the NFAT signaling pathway in tubular epithelial cells.