Oncotarget

Research Papers: Pathology:

Functional networks of aging markers in the glomeruli of IgA nephropathy: a new therapeutic opportunity

Hong Jiang, Ludan Liang, Jing Qin, Yingying Lu, Bingjue Li, Yucheng Wang, Chuan Lin, Qin Zhou, Shi Feng, Shun H. Yip, Feng Xu, EnYin Lai, Junwen Wang and Jianghua Chen _

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Oncotarget. 2016; 7:33616-33626. https://doi.org/10.18632/oncotarget.9033

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Abstract

Hong Jiang1,2,3*, Ludan Liang1,2,3*, Jing Qin5,6, Yingying Lu1,2,3, Bingjue Li1,2,3, Yucheng Wang1,2,3, Chuan Lin1,2,3, Qin Zhou1,2,3, Shi Feng1,2,3, Shun H. Yip6, Feng Xu6, EnYin Lai7, Junwen Wang4,6 and Jianghua Chen1,2,3

1 Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, P.R. China

2 Kidney Disease Immunology Laboratory, The Third Grade Laboratory, State Administration Of Traditional Chinese Medicine Of China, Hangzhou, P.R. China

3 Key Laboratory Of Multiple Organ Transplantation, Ministry Of Health, Key Laboratory Of Nephropathy, Zhejiang, P.R. China

4 Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

5 School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China

6 School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

7 Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China

* These authors have contributed equally to this work

Correspondence to:

Jianghua Chen, email:

Hong Jiang, email:

Junwen Wang, email:

Keywords: IgAN, glomerular, RNA sequence, aging, networks, Pathology Section

Received: December 12, 2015 Accepted: April 11, 2016 Published: April 26, 2016

Abstract

IgA nephropathy(IgAN) is the most common primary glomerular disease in China. Primary infections always occur before IgAN. However, the pathology of IgAN is still unclear. Previously we found that LL37, a protein secreted by senescent cells, was specific for the progression of IgAN, and also played a role in the neutrophil function. So we hypothesized that the infiltration of neutrophils, inflammation factors, and aging markers , which were modulated by functional networks, induced the immune response and renal injury. RNA-Sequencing (RNA-seq) can be used to study the whole transcriptome and detect splicing variants that are expressed in a specific cell type or tissue. We separate glomerulus from the renal biopsy tissues. After RNA extraction, the sequences were analyzed with Illumina HiSeq 2000/2500. 381 genes with differential expression between the IgAN patients and the healthy controls were identified. Only PLAU, JUN, and FOS were related to DNA damage, telomere dysfunction-induced aging markers, neutrophil function and IgA nephropathy. The networks showed the possibility of these genes being connected. We conclude that DNA damage and telomere dysfunction could play important roles in IgA nephropathy. In addition, neutrophils are also important factors in this disease. The networks of these markers showed the mechanism pathways that are involved in the duration of the occurrence and progression of IgA nephropathy and might be a new therapeutic opportunity for disease treatment.


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