High-Mobility Group Nucleosome-Binding Protein 1 Mediates Renal Fibrosis Correlating with Macrophages Accumulation and Epithelial-to-Mesenchymal Transition in Diabetic Nephropathy Mice Model
High-Mobility Group Nucleosome-Binding Protein 1 Mediates Renal Fibrosis Correlating with Macrophages Accumulation and Epithelial-to-Mesenchymal Transition in Diabetic Nephropathy Mice Model
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高迁移率组核小体结合蛋白 1 介导糖尿病肾病小鼠模型中与巨噬细胞积累和上皮间质转化相关的肾纤维化
DOI：
10.1159/000499877
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发表时间：
2019-06
影响因子：
2.8
通讯作者：
Zha Yan
中科院分区：
文献类型：
--
作者：
Yu Jiali;Dong Rong;Da Jingjing;Li Jiayu;Yu Fuxun;Zha Yan
背景/目的：肾纤维化是糖尿病肾病（DN）进展的基础。巨噬细胞在糖尿病肾脏中积累，并参与上皮-间质转化（EMT），这是导致肾纤维化的重要机制。最近，高迁移率族核小体结合蛋白1（HMGN 1）被证明在促进抗原呈递细胞的募集和激活。在这项研究中，我们首次报道了它在肾纤维化中的作用以及与巨噬细胞过滤和EMT相关的潜在机制。研究方法：20只C57 BL/6 J小鼠经链脲佐菌素（STZ）诱导糖尿病6周后，随机分为正常对照组、DN组、苯那普利组和胰岛素治疗组。采用血糖、肌酐和尿白蛋白、苏木精和伊红以及肾组织天狼星红染色评估肾脏病理学。ELISA、免疫组化和原位杂交检测HMGN 1、CD 68、F4/80、α-平滑肌肌动蛋白和E-cadherin的表达。结果如下：DN组肾脏HMGN 1、巨噬细胞标志物和EMT标志物表达水平升高，胰岛素治疗可降低这些指标的过度表达，且效果优于苯那普利治疗。两种治疗方法均不能明显改善糖尿病小鼠尿白蛋白/肌酐比值、胶原蛋白表达及肾脏组织学改变。相关性分析表明，DN小鼠HMGN 1、巨噬细胞标志物、EMT标志物和胶原表达之间存在相关性。结论：HMGN 1可能促进巨噬细胞聚集和EMT，提示其可能是预防DN肾纤维化发展的潜在治疗靶点。
Background/Aim: Renal fibrosis is essential for the progression of diabetic nephropathy (DN). Macrophages accumulate in diabetic kidneys and are involved in epithelial-to-mesenchymal transition (EMT), a vital mechanism leading to renal fibrosis. Recently, high-mobility group nucleosome-binding protein 1(HMGN1) was documented in promoting the recruitment and activation of antigen-presenting cells. In this study, we first reported its roles in renal fibrosis and the underlying mechanism associated with macrophage filtration and EMT. Methods: Twenty C57BL/6J mice were administered streptozotocin (STZ) to induce diabetes for 6 weeks and then divided into 4 groups: normal control group; DN group; benazepril-treated group, and insulin-treated group. Blood glucose, creatinine, and albumin in urine, hematoxylin and eosin, and Sirius red staining of kidney tissues were used to assess the renal pathology. ELISA, immunochemistry, and in situ hybridization were performed to determine the expression of HMGN1, CD68, F4/80, α-smooth muscle actin, and E-cadherin. Results: The renal expression levels of HMGN1, macrophage markers, and EMT makers were increased in DN group, and insulin treatment could reduce the overexpression of these indicators with a better effect than benazepril treatment. Both treatments could not obviously ameliorate urine albumin-to-creatinine ratio, collagen expression, and renal histological changes in STZ-induced diabetic mice. Correlation analysis indicated that there was a relationship among HMGN1, macrophage markers, EMT markers, and collagen expression in DN mice. Conclusion: HMGN1 may promote macrophages accumulation and EMT, suggesting a potential therapeutic target for preventing renal fibrosis development in DN.
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影响因子：
4.8
作者：
Zelmanovitz T;Gerchman F;Balthazar AP;Thomazelli FC;Matos JD;Canani LH
通讯作者：
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影响因子：
16.2
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B. Vujičić;Tamara Turk;Ž. Crnčević-Orlić;Gordana Đorđević;S. Rački
影响因子：
6
作者：
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