Integrated analysis of different microarray studies to identify candidate genes in type 1 diabetes

Jia, Xiaowei; Yu, Haotian; Zhang, Hui; Si, Yiming; Tian, Dengmei; Zhao, Xingsheng; Luan, Jing; Jia, Hao

doi:10.1111/1753-0407.12391

Cited by 9 publications

(7 citation statements)

References 38 publications

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“…Previous microarray studies listed in the GEO database that involved peripheral blood mononuclear cells (PBMCs) from type 1 diabetes patients have indicated that PLZF was a candidate gene for type 1 diabetes [ 20 ]. However, these reports did not validate the levels of PLZF protein expression.…”

Section: Discussionmentioning

confidence: 99%

Tangshen formula attenuates diabetic renal injuries by upregulating autophagy via inhibition of PLZF expression

Zhao

et al. 2017

PLoS ONE

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The Chinese herbal granule Tangshen Formula (TSF) has been proven to decrease proteinuria and improve estimated glomerular filtration rate (eGFR) in diabetic kidney disease (DKD) patients. However, the underlying mechanism of TSF on treatment of diabetic nephropathy (DN) remains unclear. The present study aimed to identify the therapeutic target of TSF in diabetic renal injuries through microarray-based gene expression profiling and establish its underlying mechanism. TSF treatment significantly attenuated diabetic renal injuries by inhibiting urinary excretion of albumin and renal histological injuries in diabetic (db/db) mice. We found that PLZF might be the molecular target of TSF in DN. In vivo, the db/db mice showed a significant increase in renal protein expression of PLZF and collagen III, and decrease in renal autophagy levels (downregulated LC3 II and upregulated p62/SQSTM1) compared to db/m mice. The application of TSF resulted in the downregulation of PLZF and collagen III and upregulation of autophagy level in the kidneys of db/db mice. In vitro, TSF reduced high glucose (HG)-induced cell proliferation for NRK52E cells. Further studies indicated that the exposure of NRK52E cells to high levels of glucose resulted in the downregulation of cellular autophagy and upregulation of collagen III protein, which was reversed by TSF treatment by decreasing PLZF expression. In conclusion, TSF might have induced cellular autophagy by inhibiting PLZF expression, which in turn resulted in an increase in autophagic degradation of collagen III that attenuated diabetic renal injuries.

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Section: Discussionmentioning

confidence: 99%

Tangshen formula attenuates diabetic renal injuries by upregulating autophagy via inhibition of PLZF expression

Zhao

et al. 2017

PLoS ONE

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“…Genes involved in metabolic processes were also affected such as Pdk4 (down 4.1-fold), a negative regulator of the pyruvate dehydrogenase complex (Zhang et al 2014). The transcription factor, Zbtb16, has been reported to be down in PBMC from T1D patients (Jia et al 2017) and was decreased 3.8-fold in prediabetic rats. The cytochrome P450 gene, Cyp2c22, was downregulated 3.5-fold as was the ER stress gene Atf3 (2.5 fold).…”

Section: Microarray Study Reveals Unique Pancreas Gene Signature In Cmentioning

confidence: 99%

Changes in insulin, glucagon and ER stress precede immune activation in type 1 diabetes

Crookshank

Serrano

Wang

et al. 2018

Journal of Endocrinology

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It is unknown whether there is a gene signature in pancreas which is associated with type 1 diabetes (T1D). We performed partial pancreatectomies on 30 day preinsulitic, diabetes-prone BioBreeding (BBdp) rats to prospectively identify factors involved in early prediabetes. Microarrays of the biopsies revealed downregulation of ER stress, metabolism and apoptosis. Based on these results, additional investigations compared gene expression in control (BBc) and BBdp rats age ~8, 30 and 60 days using RT-qPCR. Neonates had increased ER stress gene expression in pancreas. This was associated with decreased insulin, cleaved caspase-3 and Ins1 whereas Gcg and Pcsk2 were increased. The increase in ER stress was not sustained at 30 days and decreased by 60 days. In parallel, the liver gene profile showed a similar signature in neonates but with an early decrease of the unfolded protein response (UPR) at 30 days. This suggested that changes in the liver precede those in the pancreas. Tnf and Il1b expression was increased in BBdp pancreas in association with increased caspase-1, cleaved caspase-3 and decreased proinsulin area. Glucagon area was increased in both 30 day and 60 day BBdp rats. Increased co-localization of BIP and proinsulin was observed at 60 days in the pancreas, suggesting insulin-related ER dysfunction. We propose that dysregulated metabolism leads to ER stress in neonatal rats long before insulitis, creating a microenvironment in both pancreas and liver that promotes autoimmunity.

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“…Microarrays and NGS for Drug Discovery DOI: http://dx.doi.org/10.5772/intechopen.96657 are identified using integrated analysis of different microarray studies, thereby offering a new strategy for either preserving or improving β-cell function [149]. Moreover, microarray analysis has allowed for the identification of an aurora kinase A (AURKA) gene involved in cell cycle regulation that could serve as a potential biomarker for predicting poor prognosis in liposarcoma [150].…”

Section: Microarrays and Drug Discovery For Various Other Pathologiesmentioning

confidence: 99%

Microarrays and NGS for Drug Discovery

Pop¹,

Zănoagă²,

Chiroi³

et al. 2021

Drug Design - Novel Advances in the Omics Field and Applications

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Novel technologies and state of the art platforms developed and launched over the last two decades such as microarrays, next-generation sequencing, and droplet PCR have provided the medical field many opportunities to generate and analyze big data from the human genome, particularly of genomes altered by different diseases like cancer, cardiovascular, diabetes and obesity. This knowledge further serves for either new drug discovery or drug repositioning. Designing drugs for specific mutations and genotypes will dramatically modify a patient’s response to treatment. Among other altered mechanisms, drug resistance is of concern, particularly when there is no response to cancer therapy. Once these new platforms for omics data are in place, available information will be used to pursue precision medicine and to establish new therapeutic guidelines. Target identification for new drugs is necessary, and it is of great benefit for critical cases where no alternatives are available. While mutational status is of highest importance as some mutations can be pathogenic, screening of known compounds in different preclinical models offer new and quick strategies to find alternative frameworks for treating more diseases with limited therapeutic options.

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Integrated analysis of different microarray studies to identify candidate genes in type 1 diabetes

Abstract: This integrated analysis will help develop improved therapies and interventions for T1D by identifying novel drug targets.

Cited by 9 publications

References 38 publications

Tangshen formula attenuates diabetic renal injuries by upregulating autophagy via inhibition of PLZF expression

Tangshen formula attenuates diabetic renal injuries by upregulating autophagy via inhibition of PLZF expression

Changes in insulin, glucagon and ER stress precede immune activation in type 1 diabetes

Microarrays and NGS for Drug Discovery

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