scholarly journals Microarray Analysis of Long Noncoding RNAs in Female Diabetic Peripheral Neuropathy Patients

2018 ◽  
Vol 46 (3) ◽  
pp. 1209-1217 ◽  
Author(s):  
Lin Luo ◽  
Lin-Dan Ji ◽  
Jiang-Jia Cai ◽  
Mei Feng ◽  
Mi Zhou ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Signaling Pathway ◽  
Microarray Analysis ◽  
Diabetic Peripheral Neuropathy ◽  
Relevant Information ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Differentially Expressed ◽  
Qrt Pcr ◽  
Kegg Pathway Analysis

Background/Aims: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). Because of its controversial pathogenesis, DPN is still not diagnosed or managed properly in most patients. Methods: In this study, human lncRNA microarrays were used to identify the differentially expressed lncRNAs in DM and DPN patients, and some of the discovered lncRNAs were further validated in additional 78 samples by quantitative realtime PCR (qRT-PCR). Results: The microarray analysis identified 446 and 1327 differentially expressed lncRNAs in DM and DPN, respectively. The KEGG pathway analysis further revealed that the differentially expressed lncRNA-coexpressed mRNAs between DPN and DM groups were significantly enriched in the MAPK signaling pathway. The lncRNA/mRNA coexpression network indicated that BDNF and TRAF2 correlated with 6 lncRNAs. The qRT-PCR confirmed the initial microarray results. Conclusion: These findings demonstrated that the interplay between lncRNAs and mRNA may be involved in the pathogenesis of DPN, especially the neurotrophin-MAPK signaling pathway, thus providing relevant information for future studies.

scholarly journals Identification of Circular RNAs Regulating Islet β-Cell Autophagy in Type 2 Diabetes Mellitus

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Chao Bai ◽  
Wenwen Yang ◽  
Yao Lu ◽  
Wei Wei ◽  
Zongbao Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Expression Profile ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Differentially Expressed ◽  
Qrt Pcr

This study is to identify the circular RNA (circRNA) expression profile that is functionally related to pancreatic islet β-cell autophagy and their potential regulation mechanisms in type 2 diabetes mellitus (T2DM). T2DM rat model was constructed by administration of high-fat and high-sugar diet. β-cells were isolated from islets by flow cytometry. CircRNA expression profile in β-cells was detected by circRNA microarrays, and the differentially expressed circRNAs were identified and validated by qRT-PCR. MicroRNA (miRNA) target prediction software and multiple bioinformatic approaches were used to construct a map of circRNA-miRNA interactions for the differentially expressed circRNAs. A total of 825 differentially expressed circular transcripts were identified in T2DM rats compared with control rats, among which 388 were upregulated and 437 were downregulated. Ten circRNAs were identified to have significant differences by qRT-PCR. GO analysis enriched terms such as organelle membrane and protein binding and the top enriched pathways for the circRNAs included MAPK signaling pathway. The differentially expressed circRNAs might involve in MAPK signaling pathway, apoptosis, and Ras signaling pathway. We speculate that these circRNAs, especially rno_circRNA_008565, can regulate the autophagy of islet β-cells via interactions with miRNA. Dysregulation of several circRNAs may play a role in T2DM development, and rno_circRNA_008565 may be a potential regulator of β-cell autophagy.

scholarly journals Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Lin Luo ◽  
Wen-Hua Zhou ◽  
Jiang-Jia Cai ◽  
Mei Feng ◽  
Mi Zhou ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Signaling Pathway ◽  
Diabetic Peripheral Neuropathy ◽  
Cell Receptor ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Receptor Signaling ◽  
Major Mechanism ◽  
Receptor Signaling Pathway ◽  
Neurotrophin Signaling

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the “neurotrophin-MAPK signaling pathway” was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.

scholarly journals Comparative analysis of gene expression profiles in differentiated subcutaneous adipocytes between Jiaxing Black and Large White Pigs

2020 ◽  
Author(s):  
Dawei Zhang ◽  
Wenjing Wu ◽  
Xin Huang ◽  
Ke Xu ◽  
Cheng Zheng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Expression Profiles ◽  
Mapk Signaling ◽  
Fat Deposition ◽  
Mapk Signaling Pathway ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Domestic Pig ◽  
Large White ◽  
Pig Breeds

Abstract Background: Chinese domestic pig breeds are reputed for pork quality, but their low ratio of lean-to-fat carcass weight decreases production efficiency. A better understanding of the genetic regulation network of SC fat tissue is necessary for the rational selection of Chinese domestic pig breeds. In the present study, SC adipocytes were isolated from Jiaxing Black pigs (a Chinese indigenous pig breed with redundant SC fat deposition) and Large White pigs (a lean-type pig breed with relatively low SC fat deposition) and the expression profiles of mRNAs and lncRNAs were compared by RNA-seq analysis to identify biomarkers correlated with the differences of SC fat deposition between the two breeds.Results: A total of 3,371 differentially expressed genes (DEGs) and 1,182 differentially expressed lncRNAs (DELs) were identified in SC adipocytes between Jiaxing Black (JX) and Large White (LW) pigs, which included 797 upregulated mRNAs, 2,574 downregulated mRNAs, 461 upregulated lncRNAs and 721 downregulated lncRNAs. Gene Ontology and KEGG pathway analyses revealed that the DEGs and DELs were mainly involved in the immune response, cell fate determination, PI3K-Akt signaling pathway and MAPK signaling pathway, which are known to be related to adipogenesis and lipid metabolism. The expression levels of DEGs and DELs according to the RNA-seq data were verified by quantitative PCR, which showed 81.8% consistency. The differences in MAPK pathway activity between JX and LW pigs was confirmed by western blot analysis, with <100-fold elevated p38 phosphorylation in JX pigs.Conclusions: This study offers a detailed characterization of mRNAs and lncRNAs in fat- and lean-type pig breeds. The activity of the MAPK signaling pathway was found to be associated with subcutaneous adipogenesis. These results greatly enhance our understanding of the molecular mechanisms regulating SC fat deposition in pigs.

Integrative Analysis of Long Noncoding RNAs in Patients with Graft-versus-Host Disease

2020 ◽  
Vol 143 (6) ◽  
pp. 533-551 ◽  
Author(s):  
Feiyan Wang ◽  
Lan Luo ◽  
Zhenyang Gu ◽  
Nan Yang ◽  
Li Wang ◽  
...  
Keyword(s):  
B Cells ◽  
Signaling Pathway ◽  
Microarray Analysis ◽  
Graft Versus Host Disease ◽  
Differentially Expressed ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Qrt Pcr ◽  
Bcr Signaling

<b><i>Background:</i></b> Chronic graft-versus-host disease (cGVHD) remains a major cause of late non-recurrence mortality despite remarkable improvements in the field of allogeneic hematopoietic stem cell transplantation. Although recent studies have found that B-cell receptor (BCR)-activated B cells contribute to pathogenesis in cGVHD, the specific molecular mechanisms of B cells in this process remain unclear. <b><i>Methods:</i></b> In our study, human long noncoding RNA (lncRNA) microarrays and bioinformatic analysis were performed to identify different expressions of lncRNAs in peripheral blood B cells from cGVHD patients compared with healthy ones. The differential expression of lncRNA was confirmed in additional samples by quantitative real-time polymerase chain reaction (qRT-PCR). <b><i>Results:</i></b> The microarray analysis revealed that 106 of 198 differentially expressed lncRNAs were upregulated and 92 were downregulated in cGVHD patients compared with healthy controls. Intergenic lncRNAs accounted for the majority of differentially expressed lncRNAs. A KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that the differentially expressed mRNAs, which were coexpressed with lncRNA, between the cGVHD group and the healthy group were significantly enriched in the BCR signaling pathway. Further analysis of the BCR signaling pathway and its coexpression network identified three lncRNAs with the strongest correlation with BCR signaling and cGVHD, as well as a series of protein-coding genes and transcription factors associated with them. The three candidate lncRNAs were further validated in another group of cGVHD patients by qRT-PCR. <b><i>Conclusions:</i></b> This is the first study on the correlation between lncRNA and cGVHD using lncRNA microarray analysis. Our study provides novel enlightenment in exploring the molecular pathogenesis of cGVHD.

scholarly journals Identification and Characterization of MAPK Signaling Pathway Genes and Associated lncRNAs in the Ileum of Piglets Infected by Clostridium perfringens Type C

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Ruirui Luo ◽  
Xiaoyu Huang ◽  
Zunqiang Yan ◽  
Xiaoli Gao ◽  
Pengfei Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Clostridium Perfringens ◽  
Expression Patterns ◽  
Strong Support ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Differentially Expressed ◽  
Economic Losses ◽  
Sequencing Data ◽  
Type C

Clostridium perfringens type C (C. perfringens type C) is one of the main microbial pathogens responsible for piglet diarrhea worldwide, causing substantial economic losses for pig-rearing industries. The mitogen-activated protein kinase (MAPK) signaling pathway is a key regulator of inflammatory bowel disease, especially necrotic enteritis. However, whether and how the MAPK signaling pathway is involved in regulating the process of piglet diarrhea when challenged by C. perfringens type C are still unknown. Here, we screened 38 differentially expressed genes (DEGs) in piglets’ ileum tissues experimentally infected with C. perfringens type C that were enriched in the Sus scrofa MAPK signaling pathway, based on our previous transcriptome data. Of these DEGs, 12 genes (TRAF2, MAPK8, and GADD45G, among others) were upregulated whereas 26 genes (MAPK1, TP53, and CHUK, among others) were downregulated in the infected group. Our results showed that MAPK1, TP53, MAPK8, MYC, and CHUK were in the core nodes of the PPI network. Additionally, we obtained 35 lncRNAs from the sequencing data, which could be trans-targeted to MAPK signaling pathway genes and were differentially expressed in the ileum tissues infected with C. perfringens. We used qRT-PCR to verify the expression levels of genes and lncRNAs related to the MAPK signaling pathway; their expression patterns were consistent with RNA sequencing data. Our results provide strong support for deeply exploring the role of the MAPK signaling pathway in diarrhea caused by C. perfringens type C.

Cytotoxic Mechanism for Silver Nanoparticles Based High-Content Cellomics and Transcriptome Sequencing

2019 ◽  
Vol 15 (7) ◽  
pp. 1401-1414 ◽  
Author(s):  
Yan Huang ◽  
Xiaoying Lü ◽  
Xiaoqiang Lü
Keyword(s):  
Signaling Pathway ◽  
Focal Adhesion ◽  
Transcriptome Sequencing ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Differentially Expressed ◽  
Atp Content ◽  
Biological Pathway Analysis ◽  
Key Genes ◽  
Cytotoxic Mechanism

The aim of this study was to investigate the toxic mechanism for differently sized silver nanoparticles (SNPs) on human dermal fibroblasts (HDFs), by combining high content cellomics and transcriptome sequencing. First, the influences of five SNPs (SNP-5, SNP-20, SNP-50, SNP-100, and SNP-200) on O–2, focal adhesion, cytoskeleton and ATP content in HDFs were studied with high content screening and colorimetric method, and the role to cytotoxicity was analysed. Transcriptome sequencing technique was then to filter differentially expressed genes induced by SNPs after 4 h treatment. Key pathways in SNP-induced cytotoxicity were also screened via biological pathway analysis. Furthermore, key genes in HDFs after SNP-induced cytotoxicity were determined through matching analysis with previously obtained important microRNAs and their expression levels were verified with qRT-PCR. Cytological experiments showed that the SNP-5 had the strongest effects on O–2, focal adhesion, cytoskeleton and ATP content, while SNP-20 had the smallest effects. Transcriptome sequencing results showed that 3848, 4213, 2999, 3251 and 5104 genes were found to be differentially expressed in HDFs after treatment with five SNPs. Biological pathway analysis for 1643 uniformly differentially expressed genes revealed that MAPK signaling pathway was the key pathway in SNP-induced cytotoxicity. Two key genes, SOS1 and CDC25B, which are involved in MAPK signaling pathway were finally identified through matching analysis with important microRNAs and verification. In conclusion, the cytotoxic mechanism for SNPs induced cytotoxicity in HDFs involved SNPs down-regulated expression of SOS1 and CDC25B through miR-424-5p in the key MAPK signaling pathway, through blocking of cell cycle, promotion of apoptosis, ultimately leading to cytotoxicity.

Long non-coding RNA HCP5 serves as a ceRNA sponging miR-17-5p and miR-27a/b to regulate the pathogenesis of childhood obesity via the MAPK signaling pathway

2019 ◽  
Vol 32 (12) ◽  
pp. 1327-1339 ◽  
Author(s):  
Rui Chen ◽  
Guangda Xin ◽  
Xiaofei Zhang
Keyword(s):  
Childhood Obesity ◽  
Signaling Pathway ◽  
Human Leukocyte ◽  
Microarray Dataset ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Messenger Rnas ◽  
Tissue Samples

Abstract Background This study aimed to investigate the completing endogenous RNA (ceRNA) network involved in childhood obesity. Methods The microarray dataset GSE9624 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed long non-coding RNAs (lncRNAs) (DELs) and messenger RNAs (DEMs) were isolated between the childhood obesity and non-obesity tissue samples. Then, Gene Ontology (GO) functional and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of isolated DEMs were performed. DELs and DEMs targeted miRNAs were predicted to construct a ceRNA regulatory network. Finally, critical lncRNAs were validated in another dataset. Results A total of 1257 differentially expressed RNAs were screened, including 28 lncRNAs and 1229 mRNAs. In addition, these RNAs were mainly involved in defense response, cell cycle, mitogen-activated protein kinase (MAPK) signaling pathway, apoptosis, etc. Three lncRNAs (human leukocyte antigen complex 5 [HCP5], long intergenic non-protein coding RNA 839 [LINC00839] and receptor activity modifying protein 2 [RAMP2-AS1]) and two related miRNAs (hsa-miR-17-5p and hsa-miR-27a/b-3p) were identified as key RNAs in childhood obesity. Specifically, lncRNA HCP5 interacted with miR-17-5p and miR-27a/b to regulate nemo-like kinase (NLK) and Ras-related protein 2 (RRAS2) via the MAPK signaling pathway. Finally, four genes (RRAS2, NLK, bcl2/adenovirus E1B protein-interacting protein 3 [BNIP3] and phorbol-12-myristate-13-acetate-induced protein 1 [PMAIP1]) targeted by miRNAs were predicted as critical genes and might be novel diagnostic biomarkers of childhood obesity. Conclusions lncRNA HCP5 could serve as a ceRNA sponging miR-17-5p and miR-27a/b to regulate the pathogenesis of childhood obesity via NLK and RRAS2 in the MAPK signaling pathway.

scholarly journals Network Pharmacology and Molecular Docking Study on the Potential Mechanism of Yi-Qi-Huo-Xue-Tong-Luo Formula in Treating Diabetic Peripheral Neuropathy

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Yixuan Lin ◽  
Chuqiao Shen ◽  
Fanjing Wang ◽  
Zhaohui Fang ◽  
Guoming Shen
Keyword(s):  
Molecular Docking ◽  
Peripheral Neuropathy ◽  
Signaling Pathway ◽  
Diabetic Peripheral Neuropathy ◽  
Kegg Pathway ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Ppi Network ◽  
Active Ingredients ◽  
Kegg Pathway Analysis

Objective. To investigate the potential mechanism of action of Yi-Qi-Huo-Xue-Tong-Luo formula (YQHXTLF) in the treatment of diabetic peripheral neuropathy (DPN). Methods. Network pharmacology and molecular docking techniques were used in this study. Firstly, the active ingredients and the corresponding targets of YQHXTLF were retrieved using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform; subsequently, the targets related to DPN were retrieved using GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmgkb, Therapeutic Target Database (TTD) and Drugbank databases; the common targets of YQHXTLF and DPN were obtained by Venn diagram; afterwards, the “YQHXTLF Pharmacodynamic Component-DPN Target” regulatory network was visualized using Cytoscape 3.6.1 software, and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the potential targets using R 3.6.3 software. Finally, molecular docking of the main chemical components in the PPI network with the core targets was verified by Autodock Vina software. Results. A total of 86 active ingredients and 229 targets in YQHXTLF were screened, and 81 active ingredients and 110 targets were identified to be closely related to diabetic peripheral neuropathy disease. PPI network mapping identified TP53, MAPK1, JUN, and STAT3 as possible core targets. KEGG pathway analysis showed that these targets are mostly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and MAPK signaling pathway. The molecular docking results showed that the main chemical components of YQHXTLF have a stable binding activity to the core pivotal targets. Conclusion. YQHXTLF may act on TP53, MAPK1, JUN, and STAT3 to regulate inflammatory response, apoptosis, or proliferation as a molecular mechanism for the treatment of diabetic peripheral neuropathy, reflecting its multitarget and multipathway action, and providing new ideas to further uncover its pharmacological basis and mechanism of action.

MAPK: A Key Player in the Development and Progression of Stroke

2020 ◽  
Vol 19 (4) ◽  
pp. 248-256
Author(s):  
Yangmin Zheng ◽  
Ziping Han ◽  
Haiping Zhao ◽  
Yumin Luo
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Complex Disease ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Effective Prevention ◽  
Prevention And Treatment ◽  
Different Cell Types

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.

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