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足突细胞凋亡通过转化生长因子-β（TGF-β）通路在糖尿病肾病中的调节作用。

Gremlin Regulates Podocyte Apoptosis via Transforming Growth Factor-β (TGF-β) Pathway in Diabetic Nephropathy.

机构信息

Department of Nephrology, Taizhou Second People's Hospital Affiliated Yangzhou University, Taizhou, Jiangsu, China (mainland).

Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China (mainland).

出版信息

Med Sci Monit. 2018 Jan 9;24:183-189. doi: 10.12659/msm.905758.

DOI:10.12659/msm.905758
PMID:29315280
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5771160/
Abstract

BACKGROUND Gremlin has been reported to be up-regulated in glomerular mesangial cells in diabetic nephropathy (DN). However, the regulation of gremlin in podocytes is still rarely reported. This study aimed to investigate the underlying mechanisms by which gremlin mediates the pathogenesis of DN via transforming growth factor-β (TGF-β) signaling pathways. MATERIAL AND METHODS Lentiviral and RNAi transfection were performed to increase and decrease gremlin expression in high-glucose conditions. Expression at the mRNA and protein level was detected by RT-qPCR and Western blotting. RESULTS The expression of gremlin was significantly higher in high-glucose (HG, 30mM) than normal-glucose (NG, 5.5 mM) conditions. The gremlin overexpression significantly suppressed the expression of nephrin and synaptopodin. The phosphorylation of canonical TGF-b signaling pathway components, including Smad2/3 and MKK, was increased in the gremlin-overexpressing group. In addition, the expression levels of Bax and cleaved caspase-3 were also higher in the gremlin-overexpressing group. TGF-β pathway inhibitor (SB505124) significantly inhibited TGF-β pathway activity and enhanced the expression of nephrin and synaptopodin. CONCLUSIONS These results indicate that gremlin can aggravate podocyte lesions through the TGF-β signaling pathway, providing a novel therapeutic target for DN.

摘要

背景

在糖尿病肾病（DN）中，肾小球系膜细胞中的 Gremlin 被报道上调。然而，Gremlin 在足细胞中的调控作用仍鲜有报道。本研究旨在通过转化生长因子-β（TGF-β）信号通路，探讨 Gremlin 介导 DN 发病机制的潜在机制。

材料和方法

采用慢病毒和 RNAi 转染技术在高糖条件下增加和减少 Gremlin 的表达。通过 RT-qPCR 和 Western blot 检测 mRNA 和蛋白水平的表达。

结果

高糖（30mM）条件下 Gremlin 的表达明显高于正常糖（5.5mM）条件。Gremlin 的过表达显著抑制了nephrin 和 synaptopodin 的表达。Gremlin 过表达组中经典 TGF-β信号通路成分，包括 Smad2/3 和 MKK 的磷酸化水平增加。此外，Gremlin 过表达组中 Bax 和 cleaved caspase-3 的表达水平也更高。TGF-β 通路抑制剂（SB505124）显著抑制 TGF-β 通路活性并增强 nephrin 和 synaptopodin 的表达。

结论

这些结果表明，Gremlin 可以通过 TGF-β 信号通路加重足细胞损伤，为 DN 提供了一个新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfb4/5771160/687d0d807c75/medscimonit-24-183-g005.jpg
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2
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Nephron. 2015;131(1):34-42. doi: 10.1159/000438493. Epub 2015 Sep 5.
3
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恩格列净和帕立骨化醇联合治疗 2 型糖尿病小鼠的血糖控制改善和肾脏保护作用。
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4
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5
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5
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6
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7
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J Am Soc Nephrol. 2013 Jun;24(7):1088-102. doi: 10.1681/ASN.2012050445. Epub 2013 May 2.
8
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10
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