Tumor necrosis factor superfamily 14 is critical for the development of renal fibrosis.
Tumor necrosis factor superfamily 14 is critical for the development of renal fibrosis.
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肿瘤坏死因子超家族 14 对于肾纤维化的发展至关重要
DOI：
10.18632/aging.104151
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发表时间：
2020-11-24
期刊：
影响因子：
--
通讯作者：
Zhang KQ
中科院分区：
文献类型：
--
作者：
Li Y;Tang M;Han B;Wu S;Li SJ;He QH;Xu F;Li GQ;Zhang K;Cao X;Zheng QY;Chen J;Yang D;Xu GL;Zhang KQ
目的：肿瘤坏死因子超家族蛋白 14 (TNFSF14) 最近被确定为一些纤维化疾病的危险因素。然而，TNFSF14在肾纤维化发病机制中的作用仍不清楚。结果：发现与对照组相比，UUO 诱导的肾纤维化小鼠和纤维化肾病患者的 TNFSF14 水平均显着升高。因此，Tnfsf14 缺陷导致 UUO 小鼠肾纤维化病变和炎症细胞因子表达显着减少。此外，在接受 UUO 手术的 Tnfsf14 KO 小鼠中，导致纤维化肾病的关键分子 Sphk1 的水平显着降低。体外重组 TNFSF14 显着上调原代小鼠肾小管上皮细胞 (mTEC) 的 Sphk1 表达。结论:TNFSF14是一种新型的肾纤维化促纤维化因子,TNFSF14上调Sphk1表达,这可能是TNFSF14介导肾纤维化的潜在机制。方法：以单侧尿道梗阻（UUO）诱导的小鼠肾纤维化模型和纤维化肾病患者标本为研究对象，通过Masson三色染色、免疫组化、qRT-PCR和Western blot分析，探讨TNFSF14对肾纤维化的影响以及TNFSF14与促纤维化因子鞘氨醇激酶1（Sphk1）的关系。
Objective: Tumor necrosis factor superfamily protein 14 (TNFSF14) was recently identified as a risk factor in some fibrosis diseases. However, the role of TNFSF14 in renal fibrosis pathogenesis remains unknown. Results: It was found that TNFSF14 levels were significantly increased both in UUO-induced renal fibrotic mice and in patients with fibrotic nephropathy, compared with those in controls. Accordingly, Tnfsf14 deficiency led to a marked reduction in renal fibrosis lesions and inflammatory cytokines expression in the UUO mice. Furthermore, the levels of Sphk1, a critical molecule that causes fibrotic nephropathy, were remarkably reduced in Tnfsf14 KO mice with UUO surgery. In vitro recombinant TNFSF14 administration markedly up-regulated the expression of Sphk1 of primary mouse renal tubular epithelial cells (mTECs). Conclusion: TNFSF14 is a novel pro-fibrotic factor of renal fibrosis, for which TNFSF14 up-regulates Sphk1 expression, which may be the underlying mechanism of TNFSF14-mediated renal fibrosis. Methods: We investigated the effect of TNFSF14 on renal fibrosis and the relationship between TNFSF14 and pro-fibrotic factor sphingosine kinase 1 (Sphk1) by using the unilateral urethral obstruction (UUO)-induced mice renal fibrosis as a model and the specimen of patients with fibrosis nephropathy, by Masson trichrome staining, immunohistochemistry, qRT-PCR, and western blot analysis.
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DOI：
10.1038/jid.2015.110
发表时间：
2015-08
期刊：
The Journal of investigative dermatology
影响因子：
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作者：
Herro R;Antunes RDS;Aguilera AR;Tamada K;Croft M
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影响因子：
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