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Detection of differentially expressed wound-healing-related glycogenes in galectin-3-deficient mice.

ABSTRACT: PURPOSE:A prior study showed that exogenous galectin-3 (Gal-3) stimulates re-epithelialization of corneal wounds in wild-type (Gal-3(+/+)) mice but, surprisingly, not in galectin-3-deficient (Gal-3(-/-)) mice. In an effort to understand why the injured corneas of Gal-3(-/-) mice are unresponsive to exogenous Gal-3, the present study was designed to determine whether genes encoding the enzymes that regulate the synthesis of glycan ligands of Gal-3 are differentially expressed in Gal-3(-/-) corneas compared with the Gal-3(+/+) corneas. METHODS:Glycogene microarray technology was used to identify differentially expressed glycosyltransferases in healing Gal-3(+/+) and Gal-3(-/-) corneas. RESULTS:Of approximately 2000 glycogenes on the array, the expression of 8 was upregulated and that of 14 was downregulated more than 1.3-fold in healing Gal-3(-/-) corneas. A galactosyltransferase, beta3GalT5, which has the ability to synthesize Gal-3 ligands was markedly downregulated in healing Gal-3(-/-) corneas. The genes for polypeptide galactosaminyltransferases (ppGalNAcT-3 and -7) that are known to initiate O-linked glycosylation and N-aspartyl-beta-glucosaminidase, which participates in the removal of N-glycans, were found to be upregulated in healing Gal-3(-/-) corneas. Microarray data were validated by qRT-PCR. CONCLUSIONS:Based on the known functions of the differentially expressed glycogenes, it appears that the glycan structures on glycoproteins and glycolipids, synthesized as a result of the differential glycogene expression pattern in healing Gal-3(-/-) corneas may lead to the downregulation of specific counterreceptors for Gal-3. This may explain, at least in part, why, unlike healing Gal-3(+/+) corneas, the healing Gal-3(-/-) corneas are unresponsive to the stimulatory effect of exogenous Gal-3 on re-epithelialization of corneal wounds.

SUBMITTER: Saravanan C

PROVIDER: S-EPMC3005591 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Detection of differentially expressed wound-healing-related glycogenes in galectin-3-deficient mice.

Saravanan Chandrassegar C Cao Zhiyi Z Head Steven R SR Panjwani Noorjahan N

Investigative ophthalmology & visual science 20090730 12

<h4>Purpose</h4>A prior study showed that exogenous galectin-3 (Gal-3) stimulates re-epithelialization of corneal wounds in wild-type (Gal-3(+/+)) mice but, surprisingly, not in galectin-3-deficient (Gal-3(-/-)) mice. In an effort to understand why the injured corneas of Gal-3(-/-) mice are unresponsive to exogenous Gal-3, the present study was designed to determine whether genes encoding the enzymes that regulate the synthesis of glycan ligands of Gal-3 are differentially expressed in Gal-3(-/- ...[more]

PMID: 19643959

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Project description:ObjectiveWound healing is a complex process involving the coordinated interaction of various genes and molecularpathways. The study aimed to uncover novel therapeutic targets, biomarkers and candidate genes for drug developmentto improve successful wound repair interventions.Materials and Methods: This study is a network-meta analysis study. Nine wound healing microarray datasets obtainedfrom the Gene Expression Omnibus (GEO) database were used for this study. Differentially expressed genes (DEGs)were described using the Limma package and shared genes were used as input for weighted gene co-expressionnetwork analysis. The Gene Ontology analysis was performed using the EnrichR web server, and construction of aprotein-protein interaction (PPI) network was achieved by the STRING and Cytoscape.Results: A total of 424 DEGs were determined. A co-expression network was constructed using 7692 shared genesbetween nine data sets, resulting in the identification of seven modules. Among these modules, those with the top 20genes of up and down-regulation were selected. The top down-regulated genes, including TJP1, SEC61A1, PLEK,ATP5B, PDIA6, PIK3R1, SRGN, SDC2, and RBBP7, and the top up-regulated genes including RPS27A, EEF1A1,HNRNPA1, CTNNB1, POLR2A, CFL1, CSNk1E, HSPD1, FN1, and AURKB, which can potentially serve as therapeutictargets were identified. The KEGG pathway analysis found that the majority of the genes are enriched in the "Wntsignaling pathway".Conclusion: In our study of nine wound healing microarray datasets, we identified DEGs and co-expressed modulesusing WGCNA. These genes are involved in important cellular processes such as transcription, translation, and posttranslationalmodifications. We found nine down-regulated genes and ten up-regulated genes, which could serve aspotential therapeutic targets for further experimental validation. Targeting pathways related to protein synthesis and celladhesion and migration may enhance wound healing, but additional experimental validation is needed to confirm theeffectiveness and safety of targeted interventions.

Project description:IntroductionWound healing is very important for the maintenance of immune barrier integrity, which has attracted wide attention in past 10 years. However, no studies on the regulation of cuproptosis in wound healing have been reported.MethodsIn this study, the skin injury model was constructed in Gnxi goats, and the function, regulatory network and hub genes of the skin before and after the injury were comprehensively analyzed by transcriptomics.ResultsThe results showed that there were 1,438 differentially expressed genes (DEGs), genes up-regulated by 545 and genes down-regulated by 893, which were detected by comparing day 0 and day 5 posttraumatic skin. Based on GO-KEGG analysis, DEGs that were up-regulated tended to be enriched in lysosome, phagosome, and leukocyte transendothelial migration pathways, while down-regulated DEGs were significantly enriched in adrenergic signaling in cardiomyocytes and calcium signaling pathway. There were 166 overlapped genes (DE-CUGs) between DEGs and cuproptosis-related genes, with 72 up-regulated DE-CUGs and 94 down-regulated DE-CUGs. GOKEGG analysis showed that up-regulated DE-CUGs were significantly enriched in ferroptosis, leukocyte transendothelial migration and lysosome pathways, while down-regulated DE-CUGs were significantly enriched in Apelin signaling pathway and tyrosine metabolism pathways. By constructing and analyzing of protein-protein interaction (PPI) networks of DEGs and DE-CUGs, 10 hub DEGs (ENSCHIG00000020079, PLK1, AURKA, ASPM, CENPE, KIF20A, CCNB2, KIF2C, PRC1 and KIF4A) and 10 hub DE-CUGs (MMP2, TIMP1, MMP9, MMP14, TIMP3, MMP1, EDN1, GCAT, SARDH, and DCT) were obtained, respectively.DiscussionThis study revealed the hub genes and important wound healing pathways in Ganxi goats, and identified the correlation between wound healing and cuproptosis for the first time, and found that MMP2, TIMP1, MMP9, and EDN1 were the core genes associated. This study enriched the transcriptome data of wound healing in Ganxi goats and expanded the research direction of cuproptosis.

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Detection of differentially expressed wound-healing-related glycogenes in galectin-3-deficient mice.

Publications

Detection of differentially expressed wound-healing-related glycogenes in galectin-3-deficient mice.

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