scholarly journals Using High-Density SNP Array to Reveal Selection Signatures Related to Prolificacy in Chinese and Kazakhstan Sheep Breeds

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1633
Author(s):  
Yi Wang ◽  
Zhigang Niu ◽  
Zhengcheng Zeng ◽  
Yao Jiang ◽  
Yifan Jiang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Acid Metabolism ◽  
Snp Array ◽  
Enrichment Analysis ◽  
Smooth Muscle Contraction ◽  
Potential Candidate ◽  
Alpha Linolenic Acid ◽  
Hormone Synthesis ◽  
Sheep Breeds ◽  
Kegg Pathways

Selection signature provides an efficient tool to explore genes related to traits of interest. In this study, 176 ewes from one Chinese uniparous breed and three Kazakhstan multiparous breeds are genotyped using Affymetrix 600K HD single nucleotide polymorphism (SNP) arrays, F-statistics (Fst), and a Cross Population Extend Haplotype Homozygosity Test (XPEHH). These are conducted to identify genomic regions that might be under selection in three population pairs comprised the one multiparous breed and the uniparous breed. A total of 177 and 3072 common selective signatures were identified by Fst and XPEHH test, respectively. Nearly half of the common signatures detected by Fst were also captured by XPEHH test. In addition, 1337 positive and 1735 common negative signatures were observed by XPEHH in three Kazakhstan multiparous breeds. In total, 242 and 798 genes were identified in selective regions and positive selective regions identified by Fst and XPEHH, respectively. These genes were further clustered in 50 gene ontology (GO) functional terms and 66 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in enrichment analysis. The GO terms and pathways were relevant with reproductive processes, e.g., oxytocin signaling pathway, thyroid hormone synthesis and GnRH signaling pathway, vascular smooth muscle contraction and lipid metabolism (alpha-Linolenic acid metabolism and Linoleic acid metabolism), etc. Based on the findings, six potential candidate genes ESR1, OXTR, MAPK1, RYR1, PDIA4, and CYP19A1, under positive selection related to characteristics of multiparous sheep breeds were revealed. Our results improve our understanding of the mechanisms of selection that underlies the prolificacy trait in sheep, and provide essential references for future sheep breeding.

scholarly journals Dynamic characteristics and functional analysis provide new insights into long non-coding RNA responsive to Verticillium dahliae infection in Gossypium hirsutum

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guoning Wang ◽  
Xingfen Wang ◽  
Yan Zhang ◽  
Jun Yang ◽  
Zhikun Li ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Verticillium Wilt ◽  
Dynamic Characteristics ◽  
Target Genes ◽  
Acid Metabolism ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Alpha Linolenic Acid ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background Verticillium wilt is a widespread and destructive disease, which causes serious loss of cotton yield and quality. Long non-coding RNA (lncRNA) is involved in many biological processes, such as plant disease resistance response, through a variety of regulatory mechanisms, but their possible roles in cotton against Verticillium dahliae infection remain largely unclear. Results Here, we measured the transcriptome of resistant G. hirsutum following infection by V. dahliae and 4277 differentially expressed lncRNAs (delncRNAs) were identified. Localization and abundance analysis revealed that delncRNAs were biased distribution on chromosomes. We explored the dynamic characteristics of disease resistance related lncRNAs in chromosome distribution, induced expression profiles, biological function, and these lncRNAs were divided into three categories according to their induced expression profiles. For the delncRNAs, 687 cis-acting pairs and 14,600 trans-acting pairs of lncRNA-mRNA were identified, which indicated that trans-acting was the main way of Verticillium wilt resistance-associated lncRNAs regulating target mRNAs in cotton. Analyzing the regulation pattern of delncRNAs revealed that cis-acting and trans-acting lncRNAs had different ways to influence target genes. Gene Ontology (GO) enrichment analysis revealed that the regulatory function of delncRNAs participated significantly in stimulus response process, kinase activity and plasma membrane components. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that delncRNAs participated in some important disease resistance pathways, such as plant-pathogen interaction, alpha-linolenic acid metabolism and plant hormone signal transduction. Additionally, 21 delncRNAs and 10 target genes were identified as being involved in alpha-linolenic acid metabolism associated with the biosynthesis of jasmonic acid (JA). Subsequently, we found that GhlncLOX3 might regulate resistance to V. dahliae through modulating the expression of GhLOX3 implicated in JA biosynthesis. Further functional analysis showed that GhlncLOX3-silenced seedlings displayed a reduced resistance to V. dahliae, with down-regulated expression of GhLOX3 and decreased content of JA. Conclusion This study shows the dynamic characteristics of delncRNAs in multiaspect, and suggests that GhlncLOX3-GhLOX3-JA network participates in response to V. dahliae invasion. Our results provide novel insights for genetic improvement of Verticillium wilt resistance in cotton using lncRNAs.

scholarly journals A Study on the Mechanism of Milkvetch Root in the Treatment of Diabetic Nephropathy Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Chunli Piao ◽  
Qi Zhang ◽  
De Jin ◽  
Li Wang ◽  
Cheng Tang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Systems Pharmacology ◽  
Active Components ◽  
Kegg Pathways

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. Owing to its complicated pathogenesis, no satisfactory treatment strategies for DN are available. Milkvetch Root is a common traditional Chinese medicine (TCM) and has been extensively used to treat DN in clinical practice in China for many years. However, due to the complexity of botanical ingredients, the exact pharmacological mechanism of Milkvetch Root in treating DN has not been completely elucidated. The aim of this study was to explore the active components and potential mechanism of Milkvetch Root by using a systems pharmacology approach. First, the components and targets of Milkvetch Root were analyzed by using the Traditional Chinese Medicine Systems Pharmacology database. We found the common targets of Milkvetch Root and DN constructed a protein-protein interaction (PPI) network using STRING and screened the key targets via topological analysis. Enrichment of Gene Ontology (GO) pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. Subsequently, major hubs were identified and imported to the Database for Annotation, Visualization and Integrated Discovery for pathway enrichment analysis. The binding activity and targets of the active components of Milkvetch Root were verified by using the molecular docking software SYBYL. Finally, we found 20 active components in Milkvetch Root. Moreover, the enrichment analysis of GO and KEGG pathways suggested that AGE-RAGE signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway might be the key pathways for the treatment of DN; more importantly, 10 putative targets of Milkvetch Root (AKT1, VEGFA, IL-6, PPARG, CCL2, NOS3, SERPINE1, CRP, ICAM1, and SLC2A) were identified to be of great significance in regulating these biological processes and pathways. This study provides an important scientific basis for further elucidating the mechanism of Milkvetch Root in treating DN.

scholarly journals Comprehensive Analysis of Differentially Expressed Profiles of mRNA, lncRNA, and circRNA in the Uterus of Seasonal Reproduction Sheep

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 301 ◽  
Author(s):  
Yongfu La ◽  
Xiaoyun He ◽  
Liping Zhang ◽  
Ran Di ◽  
Xiangyu Wang ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Seasonal Reproduction ◽  
Hormone Synthesis ◽  
Long Photoperiod

Photoperiod is one of the important factors leading to seasonal reproduction of sheep. However, the molecular mechanisms underlying the photoperiod regulation of seasonal reproduction remain poorly understood. In this study, we compared the expression profiles of mRNAs, lncRNAs, and circRNAs in uterine tissues from Sunite sheep during three different photoperiods, namely, the short photoperiod (SP), short transfer to long photoperiod (SLP), and long photoperiod (LP). The results showed that 298, 403, and 378 differentially expressed (DE) mRNAs, 171, 491, and 499 DE lncRNAs, and 124, 270, and 400 DE circRNAs were identified between SP and LP, between SP and SLP, and between LP and SLP, respectively. Furthermore, functional enrichment analysis showed that the differentially expressed RNAs were mainly involved in the GnRH signaling pathway, thyroid hormone synthesis, and thyroid hormone signaling pathway. In addition, co-expression networks of lncRNA–mRNA were constructed based on the correlation analysis between the differentially expressed RNAs. Our study provides new insights into the expression changes of RNAs in different photoperiods, which might contribute to understanding the molecular mechanisms of seasonal reproduction in sheep.

scholarly journals A Network Pharmacology Approach to Explore the Potential Mechanisms of Yifei Sanjie Formula in Treating Pulmonary Fibrosis

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Bo Qiao ◽  
Yueying Wu ◽  
Xiaoya Li ◽  
Zhenyuan Xu ◽  
Weigang Duan ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Cell Receptor ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Kegg Pathways ◽  
Th17 Cell Differentiation ◽  
Associated Proteins ◽  
Cellular Components

Objective. Yifei Sanjie Formula (YFSJF) is an effective formula on pulmonary fibrosis (PF), which has been used in clinic for more than 30 years. In order to investigate the molecular mechanism of YFSJF in treating PF, network pharmacology was used to predict the cooperative ingredients and associated pathways. Methods. Firstly, we collected potential active ingredients of YFSJF by TCMSP databases. Secondly, we obtained PF-associated targets through OMIM and Genecards database. Finally, metascape was applied for the analysis of GO terms and KEGG pathways. Results. We screened out 76 potential active ingredients and 98 associated proteins. A total of 5715 items were obtained by GO enrichment analysis ( P < 0.05 ), including 4632 biological processes, 444 cellular components, and 639 molecular functions. A total of 143 related KEGG pathways were enriched ( P < 0.05 ), including IL-17 signaling pathway, T cell receptor signaling pathway, TNF signaling pathway, calcium signaling pathway, TH17 cell differentiation, HIF-1 signaling pathway, and PI3K-Akt signaling pathway. Conclusion. YFSJF can interfere with immune and inflammatory response through multiple targets and pathways, which has a certain role in the treatment of PF. This study lays a foundation for future experimental research.

scholarly journals Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 222
Author(s):  
Stefania D’Alessio ◽  
Stefanía Thorgeirsdóttir ◽  
Igor Kraev ◽  
Karl Skírnisson ◽  
Sigrun Lange
Keyword(s):  
Signaling Pathway ◽  
Prion Disease ◽  
Rangifer Tarandus ◽  
Extreme Environments ◽  
Estrogen Signaling ◽  
The Arctic ◽  
Receptor Interaction ◽  
Wild Female ◽  
Hormone Synthesis ◽  
Kegg Pathways

The reindeer (caribou) Rangifer tarandus is a Cervidae in the order Artiodactyla. Reindeer are sedentary and migratory populations with circumpolar distribution in the Arctic, Northern Europe, Siberia and North America. Reindeer are an important wild and domesticated species, and have developed various adaptive strategies to extreme environments. Importantly, deer have also been identified to be putative zoonotic carriers, including for parasites, prions and coronavirus. Therefore, novel insights into immune-related markers are of considerable interest. Peptidylarginine deiminases (PADs) are a phylogenetically conserved enzyme family which causes post-translational protein deimination by converting arginine into citrulline in target proteins. This affects protein function in health and disease. Extracellular vesicles (EVs) participate in cellular communication, in physiological and pathological processes, via transfer of cargo material, and their release is partly regulated by PADs. This study assessed deiminated protein and EV profile signatures in plasma from sixteen healthy wild female reindeer, collected in Iceland during screening for parasites and chronic wasting disease. Reindeer plasma EV profiles showed a poly-dispersed distribution from 30 to 400 nm and were positive for phylogenetically conserved EV-specific markers. Deiminated proteins were isolated from whole plasma and plasma EVs, identified by proteomic analysis and protein interaction networks assessed by KEGG and GO analysis. This revealed a large number of deimination-enriched pathways for immunity and metabolism, with some differences between whole plasma and EVs. While shared KEGG pathways for whole plasma and plasma EVs included complement and coagulation pathways, KEGG pathways specific for EVs were for protein digestion and absorption, platelet activation, amoebiasis, the AGE–RAGE signaling pathway in diabetic complications, ECM receptor interaction, the relaxin signaling pathway and the estrogen signaling pathway. KEGG pathways specific for whole plasma were pertussis, ferroptosis, SLE, thyroid hormone synthesis, phagosome, Staphylococcus aureus infection, vitamin digestion and absorption, and prion disease. Further differences were also found between molecular function and biological processes GO pathways when comparing functional STRING networks for deiminated proteins in EVs, compared with deiminated proteins in whole plasma. This study highlights deiminated proteins and EVs as candidate biomarkers for reindeer health and may provide information on regulation of immune pathways in physiological and pathological processes, including neurodegenerative (prion) disease and zoonosis.

scholarly journals Identification of biomarkers and pathways in hypertensive nephropathy based on the ceRNA regulatory network

2019 ◽  
Author(s):  
lei kang ◽  
Zhen Wang ◽  
Zhongjie Liu ◽  
Yingxia Liu
Keyword(s):  
Signaling Pathway ◽  
Insulin Signaling ◽  
Regulatory Network ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Insulin Signaling Pathway ◽  
Gene Set Enrichment Analysis ◽  
Chronic Hypertension ◽  
Hypertensive Nephropathy ◽  
Kegg Pathways

Abstract Background Hypertensive nephropathy (HTN) is a kind of renal injury caused by chronic hypertension, which seriously affect people’s life. The purpose of this study was to identify the potential biomarkers of HTN and understand its possible mechanisms.Methods The dataset numbered GSE28260 related to hypertensive and normotensive was downloaded from NCBI Gene Expression Omnibus. Then, the differentially expressed RNAs (DERs) were screened using R limma package, and functional analyses of DE-mRNA were performed by DAVID. Afterwards, a ceRNA network was established and KEGG pathway was analyzed based on the Gene Set Enrichment Analysis (GSEA) database. Finally, a ceRNA regulatory network directly associated with HTN was proposed.Results A total of 947 DERs were identified, including 900 DE-mRNAs, 20 DE-lncRNAs and 27 DE-miRNAs. Based on these DE-mRNAs, they were involved in biological processes such as fatty acid beta-oxidation, IRE1-mediated unfolded protein response, and transmembrane transport, and many KEGG pathways like glycine, serine and threonine metabolism, carbon metabolism. Subsequently, lncRNAs KCTD21-AS1, LINC00470 and SNHG14 were found to be hub nodes in the ceRNA regulatory network. KEGG analysis showed that insulin signaling pathway, glycine, serine and threonine metabolism, pathways in cancer, lysosome, and apoptosis was associated with hypertensive. Finally, insulin signaling pathway was screened to directly associate with HTN and was regulated by mRNAs PPP1R3C, PPKAR2B and AKT3, miRNA has-miR-107, and lncRNAs SNHG14, TUG1, ZNF252P-AS1 and MIR503HG.Conclusions Insulin signaling pathway was directly associated with HTN, and miRNA has-miR-107 and lncRNAs SNHG14, TUG1, ZNF252P-AS1 and MIR503HG were the biomarkers of HTN. These results would improve our understanding of the occurrence and development of HTN.

scholarly journals Weighted Gene Co-Expression Network Analysis revealed key biomarkers associated with the diagnosis of hypertrophic cardiomyopathy

2020 ◽  
Author(s):  
Xin Li ◽  
Chenxin Wang ◽  
Xiaoqing Zhang ◽  
Jiali Liu ◽  
Yu Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Roc Curves ◽  
R Package ◽  
Diagnostic Value ◽  
Wilcoxon Test ◽  
Hub Genes ◽  
Kegg Pathways ◽  
Ppar Signaling

Abstract Objective: To reveal the molecular mechanism underlying the pathogenesis of HCM and find new effective therapeutic strategies using a systematic biological approach.Methods: The WGCNA algorithm was applied to building the co-expression network of HCM samples. A sample cluster analysis was performed using the hclust tool and a co-expression module was constructed. The WGCNA algorithm was used to study the interactive connection between co-expression modules and draw a heat map to show the strength of interactions between modules. The genetic information of the respective modules was mapped to the associated GO terms and KEGG pathways, and the Hub Genes with the highest connectivity in each module were identified. The Wilcoxon test was used to verify the expression level of hub genes between HCM and normal samples, and the "pROC" R package was used to verify the possibility of hub genes as biomarkers. Finally, the potential functions of hub genes were analyzed by GSEA software. Results: Seven co-expression modules were constructed using sample clustering analysis. GO and KEGG enrichment analysis judged that the turquoise module is an important module. The hub genes of each module are RPL35A for module Black, FH for module Blue, PREI3 for module Brown, CREB1 for module Green, LOC641848 for module Pink, MYH7 for module Turquoise and MYL6 for module Yellow. The results of the differential expression analysis indicate that MYH7 and FH are considered true hub genes. In addition, the ROC curves revealed their high diagnostic value as biomarkers for HCM. Finally, in the results of the GSEA analysis, MYH7 and FH highly expressed genes were enriched with the "proteasome" and a "PPAR signaling pathway," respectively.Conclusions: The MYH7 and FH genes may be the true hub genes of HCM. Their respective enriched pathways, namely the "proteasome" and the "PPAR signaling pathway," may play an important role in the development of HCM.

scholarly journals Identification and Characterization of MiRNAs in Coccomyxa subellipsoidea C-169

2019 ◽  
Vol 20 (14) ◽  
pp. 3448
Author(s):  
Runqing Yang ◽  
Gu Chen ◽  
Huifeng Peng ◽  
Dong Wei
Keyword(s):  
High Throughput Sequencing ◽  
Target Genes ◽  
Acid Metabolism ◽  
Biofuel Production ◽  
Transcriptional Level ◽  
Alpha Linolenic Acid ◽  
Kegg Pathways ◽  
Coccomyxa Subellipsoidea ◽  
Potential Impact

Coccomyxa subellipsoidea C-169 (C-169) is an oleaginous microalga which is promising for renewable biofuel production. MicroRNAs (miRNAs), as the pivotal modulators of gene expression at post-transcriptional level, are prospective candidates for bioengineering practice. However, so far, no miRNA in C-169 has been reported and its potential impact upon CO2 supplementation remains unclear. High-throughput sequencing of small RNAs from C-169 cultured in air or 2% CO2 revealed 124 miRNAs in total, including 118 conserved miRNAs and six novel ones. In total, 384 genes were predicted as their potential target genes, 320 for conserved miRNAs and 64 for novel miRNAs. The annotated target genes were significantly enriched in six KEGG pathways, including pantothenate and CoA biosynthesis, C5-branched dibasic acid metabolism, 2-oxocarboxylic acid metabolism, butanoate metabolism, valine, leucine and isoleucine biosynthesis and alpha-linolenic acid metabolism. The miRNAs’ target genes were enriched in lipid metabolism as well as RNA-interacting proteins involved in translation, transcription and rRNA processing. The pioneering identification of C-169 miRNAs and analysis of their putative target genes lay the foundation for further miRNA research in eukaryotic algae and will contribute to the development of C-169 as an oleaginous microalga through bioengineering in the future.

Bufalin: A Systematic Review of Research Hotspots and Antitumor Mechanisms by Text Mining and Bioinformatics

2020 ◽  
Vol 48 (07) ◽  
pp. 1633-1650
Author(s):  
Xian Zhang ◽  
Xiaoxuan Zhao ◽  
Kaili Liu ◽  
Yuxuan Che ◽  
Xun Qiu ◽  
...  
Keyword(s):  
Network Analysis ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Kegg Pathways ◽  
Mesh Terms ◽  
Go Enrichment ◽  
Pubmed Database ◽  
Pathways Analysis

Bufalin is an anticancer drug extract from traditional Chinese medicine. Several articles about bufalin have been published. However, the literature on bufalin has not yet been systematically studied. This study aimed to identify the study status and knowledge structures of bufalin and to summarize the antitumor mechanism. Data were retrieved and downloaded from the PubMed database. The softwares of BICOMB, gCLUTO, Ucinet 6.0, and NetDraw2.084 were used to analyze these publications. The bufalin related genes were recognized and tagged by ABNER software. Then these BF-related genes were performed by Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, and protein-protein interaction (PPI) network analysis. A total of 474 papers met the search criteria from 2000 to 2019. By biclustering clustering analysis, the 50 high-frequency main MeSH terms/subheadings were classified into 5 clusters. The clusters of drug therapy and the mechanism of bufalin were hotspot topics. A total of 50 genes were identified as BF-related genes. PPI network analysis showed that inducing apoptosis was the main effect of bufalin, and apoptosis-related gene Caspase 3 was the most reported by people. Bufalin could inhibit the proliferation, invasion, and metastasis of cancer cells through multiple signaling pathways, such as PI3K/AKT, Hedgehog, MAPK/JNK, Wnt/[Formula: see text]-catenin, TGF-[Formula: see text]/Smad, Integrin signaling pathway, and NF-KB signaling pathway via KEGG analysis. Through the quantitative analysis of bufalin literature, we revealed the research status and hot spots in this field and provided some guidance for further research.

scholarly journals Dynamics and Functional Interplay of Non-histone Lysine Crotonylome and Ubiquitylome in Vascular Smooth Muscle Cell Phenotypic Remodeling

2021 ◽  
Author(s):  
Shan-Hu Cao ◽  
Zhi-Huan Chen ◽  
Lin Yue ◽  
Han-Mei Jiang ◽  
Ru-Yuan Ma ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Smooth Muscle Contraction ◽  
Akt Signaling Pathway ◽  
Nonhistone Proteins ◽  
Ubiquitinated Proteins ◽  
Vascular Smooth Muscle Contraction

Abstract BackgroundsCrotonylation of histones is a recently discovered type of post-translational modification that can regulate gene expression. However, the function of crotonylation on nonhistone proteins in vascular smooth muscle cells (VSMC) is unclear. Here, we aim to use modification and proteomic analysis to find the cellular characteristic of crotonylated nonhistone proteins and the crosstalk with ubiquitinated proteins in vascular smooth muscle cell (VSMC) phenotypic remodeling. ResultsWe performed modification and proteomic analysis of VSMCs before and after platelet-derived growth factor-BB (PDGF-BB) stimulation. The crotonylated and ubiquitinated pan-antibody was used to enrich the protein and then subjected to high-throughput mass spectrometry analysis. Then we compared the enrichment analysis of differentially modified proteins in regards to GO terms, KEGG pathway and protein domain. As a result, there were 2138 crotonylation sites in 534 proteins and 1359 ubiquitination sites corresponding to 657 proteins. The crotonylated proteins participate in a variety of important cellular pathways and perform different functions in VSMCs. Among them, some proteins were found to be closely involved in the physiological process of VSMC phenotypic remodeling including glycolysis/gluconeogenesis, vascular smooth muscle contraction, and PI3K-Akt signaling pathway. Furthermore, the KEGG pathway enrichment analysis showed that the ubiquitinated proteins were found to be closely involved in the physiological process of VSMC phenotypic remodeling including glycolysis/gluconeogenesis, vascular smooth muscle contraction, RAS signaling pathway or PI3K-Akt signaling pathway. Crosstalk analysis showed that there were 199 sites within 177 proteins modified by crotonylation and ubiquitination simultaneously. PPI network analysis indicated that crotonylated and ubiquitinated proteins played an important role in cellular bioprocess commonly and possible synergistic effect. ConclusionsIn summary, our bioinformatics show that nonhistone crotonylation and ubiquitination play an important role in the VSMC phenotypic transformation induced by PDGF-BB stimulation. The crosstalk of crotonylation and ubiquitination in glycolysis is possibly a novel mechanism underlying the VSMC phenotypic remodeling.

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