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DENDRIN在几种肾小球疾病中的表达及其与病理参数和肾衰竭的相关性——初步研究

Expression of DENDRIN in several glomerular diseases and correlation to pathological parameters and renal failure - preliminary study.

作者信息

Mizdrak Maja, Vukojević Katarina, Filipović Natalija, Čapkun Vesna, Benzon Benjamin, Durdov Merica Glavina

机构信息

Department of Nephrology and Hemodialysis, University Hospital Centre Split, Šoltanska 1, 21000, Split, Croatia.

Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Split, Croatia.

出版信息

Diagn Pathol. 2018 Nov 20;13(1):90. doi: 10.1186/s13000-018-0767-z.

DOI:10.1186/s13000-018-0767-z
PMID:30458823
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6247684/
Abstract

BACKGROUND

In glomerular injury dendrin translocates from the slit diaphragm to the podocyte nucleus, inducing apoptosis. We analyzed dendrin expression in IgA glomerulonephritis and Henoch Schönlein purpura (IgAN/HSP) versus in podocytopathies minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), and compared it to pathohistological findings and renal function at the time of biopsy and the last follow-up.

METHODS

Twenty males and 13 females with median of age 35 years (min-max: 3-76) who underwent percutaneous renal biopsy and had diagnosis of glomerular disease (GD) were included in this retrospective study. Fifteen patients had IgAN/HSP and eighteen podocytopathy. Control group consisted of ten patients who underwent nephrectomy due to renal cancer. Dendrin expression pattern (membranous, dual, nuclear or negative), number of dendrin positive nuclei and proportion of dendrin negative glomeruli were analyzed.

RESULTS

In GD and the control group significant differences in number of dendrin positive nuclei and proportion of dendrin negative glomeruli were found (P = 0.004 and P = 0.003, respectively). Number of dendrin positive nuclei was higher in podocytopathies than in IgAN/HSP, 3.90 versus 1.67 (P = 0.028). Proportion of dendrin negative glomeruli correlated to higher rates of interstitial fibrosis (P = 0.038), tubular atrophy (P = 0.011) and globally sclerotic glomeruli (P = 0.008). Dual and nuclear dendrin expression pattern were connected with lower rate of interstitial fibrosis and tubular atrophy than negative dendrin expression pattern (P = 0.024 and P = 0.017, respectively). Proportion of dendrin negative glomeruli correlated with lower creatinine clearance (CC) at the time of biopsy and the last follow-up (P = 0.010 and P < 0.001, respectively). Dendrin expression pattern correlated to CC at the last follow-up (P = 0.009), being lower in patients with negative than nuclear or dual dendrin expression (P = 0.034 and P = 0.004, respectively).

CONCLUSION

In this pilot study the number of dendrin positive nuclei was higher in podocytopathies than in inflammatory GD. Negative dendrin expression pattern correlated to chronic tubulointerstitial changes and lower CC, which needs to be confirmed in a larger series.

摘要

背景

在肾小球损伤中,树突蛋白从裂孔隔膜转移至足细胞核,诱导细胞凋亡。我们分析了IgA肾小球肾炎和过敏性紫癜(IgAN/HSP)与足细胞病微小病变肾病(MCD)和局灶节段性肾小球硬化(FSGS)中树突蛋白的表达情况,并将其与活检时及末次随访时的病理组织学结果和肾功能进行比较。

方法

本回顾性研究纳入了20例男性和13例女性,年龄中位数为35岁(最小-最大:3-76岁),均接受了经皮肾活检并被诊断为肾小球疾病(GD)。15例患者为IgAN/HSP,18例为足细胞病。对照组由10例因肾癌接受肾切除术的患者组成。分析树突蛋白的表达模式(膜性、双重、核性或阴性)、树突蛋白阳性核的数量以及树突蛋白阴性肾小球的比例。

结果

在GD组和对照组中,发现树突蛋白阳性核的数量和树突蛋白阴性肾小球的比例存在显著差异(分别为P = 0.004和P = 0.003)。足细胞病中树突蛋白阳性核的数量高于IgAN/HSP,分别为3.90和1.67(P = 0.028)。树突蛋白阴性肾小球的比例与更高的间质纤维化率(P = 0.038)、肾小管萎缩率(P = 0.011)和全球硬化性肾小球率(P = 0.008)相关。与阴性树突蛋白表达模式相比,双重和核性树突蛋白表达模式与较低的间质纤维化率和肾小管萎缩率相关(分别为P = 0.024和P = 0.017)。树突蛋白阴性肾小球的比例与活检时及末次随访时较低的肌酐清除率(CC)相关(分别为P = 0.010和P < 0.001)。树突蛋白表达模式与末次随访时的CC相关(P = 0.009),阴性树突蛋白表达的患者的CC低于核性或双重树突蛋白表达的患者(分别为P = 0.034和P = 0.004)。

结论

在这项初步研究中,足细胞病中树突蛋白阳性核的数量高于炎症性GD。阴性树突蛋白表达模式与慢性肾小管间质改变和较低的CC相关,这需要在更大的系列研究中得到证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97dd/6247684/969e5119e224/13000_2018_767_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97dd/6247684/f05f3e8683cf/13000_2018_767_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97dd/6247684/03ff8087d3b4/13000_2018_767_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97dd/6247684/969e5119e224/13000_2018_767_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97dd/6247684/f05f3e8683cf/13000_2018_767_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97dd/6247684/03ff8087d3b4/13000_2018_767_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97dd/6247684/969e5119e224/13000_2018_767_Fig3_HTML.jpg

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Wtip- and gadd45a-interacting protein dendrin is not crucial for the development or maintenance of the glomerular filtration barrier.Wtip- 和 gadd45a 相互作用蛋白 dendrin 对于肾小球滤过屏障的发育或维持不是至关重要的。
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