Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of Chronic Kidney Disease

Background/Aims: Chronic kidney disease (CKD) is a worldwide public health problem. Regardless of the underlying primary disease, CKD tends to progress to end-stage kidney disease, resulting in unsatisfactory and costly treatment. Its common pathogenesis, however, remains unclear. The aim of this st...

Full description

Bibliographic Details
Main Authors: Le-Ting Zhou, Shen Qiu, Lin-Li Lv, Zuo-Lin Li, Hong Liu, Ri-Ning Tang, Kun-Ling Ma, Bi-Cheng Liu
Format: Article
Language:English
Published: Karger Publishers 2018-04-01
Series:Kidney & Blood Pressure Research
Subjects:
Online Access:https://www.karger.com/Article/FullText/488830
_version_ 1828462222494400512
author Le-Ting Zhou
Shen Qiu
Lin-Li Lv
Zuo-Lin Li
Hong Liu
Ri-Ning Tang
Kun-Ling Ma
Bi-Cheng Liu
author_facet Le-Ting Zhou
Shen Qiu
Lin-Li Lv
Zuo-Lin Li
Hong Liu
Ri-Ning Tang
Kun-Ling Ma
Bi-Cheng Liu
author_sort Le-Ting Zhou
collection DOAJ
description Background/Aims: Chronic kidney disease (CKD) is a worldwide public health problem. Regardless of the underlying primary disease, CKD tends to progress to end-stage kidney disease, resulting in unsatisfactory and costly treatment. Its common pathogenesis, however, remains unclear. The aim of this study was to provide an unbiased catalog of common gene-expression changes of CKD and reveal the underlying molecular mechanism using an integrative bioinformatics approach. Methods: We systematically collected over 250 Affymetrix microarray datasets from the glomerular and tubulointerstitial compartments of healthy renal tissues and those with various types of established CKD (diabetic kidney disease, hypertensive nephropathy, and glomerular nephropathy). Then, using stringent bioinformatics analysis, shared differentially expressed genes (DEGs) of CKD were obtained. These shared DEGs were further analyzed by the gene ontology (GO) and pathway enrichment analysis. Finally, the protein-protein interaction networks(PINs) were constructed to further refine our results. Results: Our analysis identified 176 and 50 shared DEGs in diseased glomeruli and tubules, respectively, including many transcripts that have not been previously reported to be involved in kidney disease. Enrichment analysis also showed that the glomerular and tubulointerstitial compartments underwent a wide range of unique pathological changes during chronic injury. As revealed by the GO enrichment analysis, shared DEGs in glomeruli were significantly enriched in exosomes. By constructing PINs, we identified several hub genes (e.g. OAS1, JUN, and FOS) and clusters that might play key roles in regulating the development of CKD. Conclusion: Our study not only further reveals the unifying molecular mechanism of CKD pathogenesis but also provides a valuable resource of potential biomarkers and therapeutic targets.
first_indexed 2024-12-11T02:32:14Z
format Article
id doaj.art-7189836e388e42d0a38c9e647d3fc8af
institution Directory Open Access Journal
issn 1420-4096
1423-0143
language English
last_indexed 2024-12-11T02:32:14Z
publishDate 2018-04-01
publisher Karger Publishers
record_format Article
series Kidney & Blood Pressure Research
spelling doaj.art-7189836e388e42d0a38c9e647d3fc8af2022-12-22T01:23:48ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432018-04-0143256858110.1159/000488830488830Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of Chronic Kidney DiseaseLe-Ting ZhouShen QiuLin-Li LvZuo-Lin LiHong LiuRi-Ning TangKun-Ling MaBi-Cheng LiuBackground/Aims: Chronic kidney disease (CKD) is a worldwide public health problem. Regardless of the underlying primary disease, CKD tends to progress to end-stage kidney disease, resulting in unsatisfactory and costly treatment. Its common pathogenesis, however, remains unclear. The aim of this study was to provide an unbiased catalog of common gene-expression changes of CKD and reveal the underlying molecular mechanism using an integrative bioinformatics approach. Methods: We systematically collected over 250 Affymetrix microarray datasets from the glomerular and tubulointerstitial compartments of healthy renal tissues and those with various types of established CKD (diabetic kidney disease, hypertensive nephropathy, and glomerular nephropathy). Then, using stringent bioinformatics analysis, shared differentially expressed genes (DEGs) of CKD were obtained. These shared DEGs were further analyzed by the gene ontology (GO) and pathway enrichment analysis. Finally, the protein-protein interaction networks(PINs) were constructed to further refine our results. Results: Our analysis identified 176 and 50 shared DEGs in diseased glomeruli and tubules, respectively, including many transcripts that have not been previously reported to be involved in kidney disease. Enrichment analysis also showed that the glomerular and tubulointerstitial compartments underwent a wide range of unique pathological changes during chronic injury. As revealed by the GO enrichment analysis, shared DEGs in glomeruli were significantly enriched in exosomes. By constructing PINs, we identified several hub genes (e.g. OAS1, JUN, and FOS) and clusters that might play key roles in regulating the development of CKD. Conclusion: Our study not only further reveals the unifying molecular mechanism of CKD pathogenesis but also provides a valuable resource of potential biomarkers and therapeutic targets.https://www.karger.com/Article/FullText/488830MicroarrayProtein– protein interaction networkChronic kidney diseaseBioinformaticsMolecular mechanisms
spellingShingle Le-Ting Zhou
Shen Qiu
Lin-Li Lv
Zuo-Lin Li
Hong Liu
Ri-Ning Tang
Kun-Ling Ma
Bi-Cheng Liu
Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of Chronic Kidney Disease
Kidney & Blood Pressure Research
Microarray
Protein– protein interaction network
Chronic kidney disease
Bioinformatics
Molecular mechanisms
title Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of Chronic Kidney Disease
title_full Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of Chronic Kidney Disease
title_fullStr Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of Chronic Kidney Disease
title_full_unstemmed Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of Chronic Kidney Disease
title_short Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of Chronic Kidney Disease
title_sort integrative bioinformatics analysis provides insight into the molecular mechanisms of chronic kidney disease
topic Microarray
Protein– protein interaction network
Chronic kidney disease
Bioinformatics
Molecular mechanisms
url https://www.karger.com/Article/FullText/488830
work_keys_str_mv AT letingzhou integrativebioinformaticsanalysisprovidesinsightintothemolecularmechanismsofchronickidneydisease
AT shenqiu integrativebioinformaticsanalysisprovidesinsightintothemolecularmechanismsofchronickidneydisease
AT linlilv integrativebioinformaticsanalysisprovidesinsightintothemolecularmechanismsofchronickidneydisease
AT zuolinli integrativebioinformaticsanalysisprovidesinsightintothemolecularmechanismsofchronickidneydisease
AT hongliu integrativebioinformaticsanalysisprovidesinsightintothemolecularmechanismsofchronickidneydisease
AT riningtang integrativebioinformaticsanalysisprovidesinsightintothemolecularmechanismsofchronickidneydisease
AT kunlingma integrativebioinformaticsanalysisprovidesinsightintothemolecularmechanismsofchronickidneydisease
AT bichengliu integrativebioinformaticsanalysisprovidesinsightintothemolecularmechanismsofchronickidneydisease