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狼疮性肾炎患者足细胞中线粒体分裂蛋白的过度产生与线粒体分裂

Overproduction of Mitochondrial Fission Proteins and Mitochondrial Fission in Podocytes of Lupus Nephritis Patients.

作者信息

Wei Qijiao, Wu Xinchen, Chen Zhihan, Lin He, Xiong Lei, Wang Na

机构信息

Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, 201102, People's Republic of China.

The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, People's Republic of China.

出版信息

J Inflamm Res. 2024 Dec 10;17:10807-10818. doi: 10.2147/JIR.S497813. eCollection 2024.

DOI:10.2147/JIR.S497813
PMID:39677288
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11645915/
Abstract

BACKGROUND

The glomerular injury is associated with different pathogeneses, and podocyte damage is common in various ISN/RPS class lupus nephritis (LN). In podocyte, mitochondrial morphological changes are observed in lupus nephritis (LN) in our previous study. This study aimed to explore mitochondrial fission proteins expression in podocytes using bioinformatics analysis and further to investigate the associations between mitochondrial fission proteins and laboratory features in LN.

METHODS

To determine the differentially expressed genes (DEGs) between LN and normal controls, we downloaded and analyzed microarray datasets. Then download the mitochondrial genes list from the MitoMiner 4.0 database, then take the genes that are common with the DEGs. Functional enrichment analyses were then performed. Then mitochondrial fission was observed through electron microscope. We performed immunofluorescence staining to explore the expression of mitochondrial fission proteins in LN patients.

RESULTS

Among these 658 DEGs, 5 DEGs related to mitochondrial dynamics were identified. Mitochondrial dynamics proteins were involved in mitophagy. Mitochondrial fission proteins Drp1 and Fis1 staining were significantly enhanced compared to that in the controls. 24h-UTP are positively correlated with mitochondrial fission proteins expression.

CONCLUSION

Mitochondrial fission was observed in LN patients' podocytes. Mitochondrial fission proteins Drp1 and Fis1 were overproduced in podocytes, and then they can lead to mitochondrial fission, which may aggravate podocyte damage and proteinuria. While the mechanism still needs to be explored.

摘要

背景

肾小球损伤与不同的发病机制相关，足细胞损伤在各种国际肾脏病学会/肾脏病理学会（ISN/RPS）分类的狼疮性肾炎（LN）中很常见。在我们之前的研究中，在狼疮性肾炎（LN）患者的足细胞中观察到线粒体形态变化。本研究旨在通过生物信息学分析探索足细胞中线粒体分裂蛋白的表达，并进一步研究线粒体分裂蛋白与LN患者实验室特征之间的关联。

方法

为了确定LN患者与正常对照之间的差异表达基因（DEG），我们下载并分析了微阵列数据集。然后从MitoMiner 4.0数据库下载线粒体基因列表，接着选取与DEG共有的基因。随后进行功能富集分析。然后通过电子显微镜观察线粒体分裂。我们进行免疫荧光染色以探索LN患者中线粒体分裂蛋白的表达。

结果

在这658个DEG中，鉴定出5个与线粒体动力学相关的DEG。线粒体动力学蛋白参与了线粒体自噬。与对照组相比，线粒体分裂蛋白Drp1和Fis1的染色显著增强。24小时尿蛋白（24h-UTP）与线粒体分裂蛋白的表达呈正相关。

结论

在LN患者的足细胞中观察到线粒体分裂。足细胞中线粒体分裂蛋白Drp1和Fis1过度产生，进而可导致线粒体分裂，这可能会加重足细胞损伤和蛋白尿。不过其机制仍有待探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/08409a56bac1/JIR-17-10807-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/d37f7d739ed1/JIR-17-10807-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/7b728ff76b32/JIR-17-10807-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/e2705b6f7e03/JIR-17-10807-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/383230d0d98b/JIR-17-10807-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/470648d345ec/JIR-17-10807-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/2e9aa760e56d/JIR-17-10807-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/e54bd77d139a/JIR-17-10807-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/08409a56bac1/JIR-17-10807-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/d37f7d739ed1/JIR-17-10807-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/7b728ff76b32/JIR-17-10807-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/e2705b6f7e03/JIR-17-10807-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/383230d0d98b/JIR-17-10807-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/470648d345ec/JIR-17-10807-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/2e9aa760e56d/JIR-17-10807-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/e54bd77d139a/JIR-17-10807-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053b/11645915/08409a56bac1/JIR-17-10807-g0008.jpg

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Gene Regulation Network of Prognostic Biomarker YAP1 in Human Cancers: An Integrated Bioinformatics Study.人类癌症中预后生物标志物 YAP1 的基因调控网络：一项综合生物信息学研究。
Pathol Oncol Res. 2021 Jun 11;27:1609768. doi: 10.3389/pore.2021.1609768. eCollection 2021.
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Gene Expression Profiling in the Skin Reveals Strong Similarities between Subacute and Chronic Cutaneous Lupus that Are Distinct from Lupus Nephritis.
皮肤基因表达谱分析显示亚急性和慢性皮肤狼疮之间具有很强的相似性，与狼疮肾炎不同。
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Downregulation of Drp1 and Fis1 Inhibits Mitochondrial Fission and Prevents High Glucose-Induced Apoptosis in Retinal Endothelial Cells.下调 Drp1 和 Fis1 抑制线粒体分裂并防止高糖诱导的视网膜内皮细胞凋亡。
Cells. 2020 Jul 10;9(7):1662. doi: 10.3390/cells9071662.
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Lupus nephritis.狼疮性肾炎。
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