| Renalase对肾小管上皮细胞-间充质转分化影响的研究 |
| 投稿时间：2016-11-13 修订日期：2016-11-27 点此下载全文 |
| 引用本文：吴逸如,王丽妍,邓岱,张启东,刘文虎.Renalase对肾小管上皮细胞-间充质转分化影响的研究[J].医学研究杂志,2017,46(7):20-25,19 |
| DOI：
10.11969/j.issn.1673-548X.2017.07.006 |
| 摘要点击次数: 1087 |
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| 基金项目:国家自然科学基金资助项目（81570660）；北京市科技计划项目（D131100004713001） |
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| 中文摘要:目的 本研究旨在探讨Renalase是否可以延缓肾脏纤维化。方法 体外培养人近端肾小管上皮细胞，给予TGF-β1和（或）不同浓度的Renalase与细胞共同孵育，观察细胞形态的变化，应用免疫荧光观察E-cadherin、α-SMA的分布和表达情况；应用Western blot（WB）法和RT-PCR检测细胞中E-cadherin、α-SMA的蛋白和mRNA表达，应用WB检测FN和Col-Ⅰ蛋白表达，并检测细胞内信号分子p-Smad-2/3、p-ERK1/2、p-p38水平的变化，探讨其可能的分子生物学机制。结果 给予TGF-β1刺激后，E-cadherin表达下调、α-SMA、FN、Col-Ⅰ表达增加。应用不同浓度Renalase与TGF-β1共孵育细胞，上述现象改善，且呈剂量依赖性。同时，与单独TGF-β1刺激相比，添加Renalase共孵育后，细胞内p-smad 2/3和p-p38表达无明显变化，但p-ERK 1/2表达明显下调，差异有统计学意义。而应用质粒转染过表达ERK信号通路后，Renalase抑制TGF-β1诱导的EMT和纤维化的作用被抵消。结论 本研究首次证实Renalase可以减轻TGF-β1所致的肾小管上皮细胞间充质转分化和纤维化，其机制可能与抑制ERK 1/2信号通路的激活相关，为临床延缓CKD进展提供新的治疗靶点和理论依据。 |
| 中文关键词:Renalase 上皮细胞间充质转分化 肾脏纤维化 ERK信号通路 |
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| Effects of renalase on Renal Tubular Epithelial-mesenchymal Transdifferentiation |
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| Abstract:Objective To explore whether Renalase can delay renal fibrosis. Methods Human proximal renal tubular epithelial cells were cultured in vitro and incubated with TGF-β1 with or without various concentrations of Renalase. The expression of E-cadherin, α-SMA, FN, Col-Ⅰ was detected by different methods to evaluate the level of EMT and fibtosis. Then, the expression of p-Smad 2/3, p-ERK 1/2 and p-p38 was detected by Western blot(WB) to explore the possible molecular biological mechanism. Results The expression of E-cadherin, α-SMA, FN and Col-Ⅰ increased after TGF-β1 stimulation. When incubated with different concentrations of Renalase, the appeal phenomenon was improved in a dose-dependent manner. The expression of p-smad 2/3 and p-p38 in the cells incubated with Renalase was almost the same with that of TGF-β1 alone, while the expression of p-ERK 1/2 was significantly down-regulated. When ERK signaling pathways was overexpressed, the inhibition of Renalase in TGF-β1-induced EMT and fibrosis role was offset. Conclusion Renalase can reduce TGF-β1-induced renal tubular epithelial-mesenchymal transition and fibrosis in a dose-dependent manner. This mechanism may be related to the inhibition of ERK 1/2 signaling pathway activation,which provides a new therapeutic target and theoretical basis for the clinical development of delayed CKD. |
| keywords:Renalase Epithelial mesenchymal transdifferentiation Renal fibrosis ERK signaling pathway |
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