دورية أكاديمية

Bioinformatics proved the existence of potential hub genes activating autophagy to participate in cartilage degeneration in osteonecrosis of the femoral head.

التفاصيل البيبلوغرافية
العنوان: Bioinformatics proved the existence of potential hub genes activating autophagy to participate in cartilage degeneration in osteonecrosis of the femoral head.
المؤلفون: Zhu Y; Department of Orthopedics, The Second Affiliated Hospital of Xi' an Jiaotong University, Xi'an, 710004, China., Wang X; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada., Liu R; Department of Orthopedics, The Second Affiliated Hospital of Xi' an Jiaotong University, Xi'an, 710004, China. liuryu@126.com.
المصدر: Journal of molecular histology [J Mol Histol] 2024 Aug; Vol. 55 (4), pp. 539-554. Date of Electronic Publication: 2024 May 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Netherlands Country of Publication: Netherlands NLM ID: 101193653 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1567-2387 (Electronic) Linking ISSN: 15672379 NLM ISO Abbreviation: J Mol Histol Subsets: MEDLINE
أسماء مطبوعة: Publication: Dordrecht, The Netherlands : Springer Netherlands
Original Publication: Dordrecht, The Netherlands : Kluwer Academic Publishers, 2004-
مواضيع طبية MeSH: Autophagy*/genetics , Computational Biology*/methods , Protein Interaction Maps*/genetics , Gene Regulatory Networks* , Femur Head Necrosis*/genetics , Femur Head Necrosis*/pathology , Femur Head Necrosis*/metabolism, Humans ; Gene Expression Profiling ; Chondrocytes/metabolism ; Chondrocytes/pathology ; Cartilage, Articular/metabolism ; Cartilage, Articular/pathology ; Femur Head/pathology ; Femur Head/metabolism ; Gene Expression Regulation ; Databases, Genetic ; Autophagy-Related Proteins/genetics ; Autophagy-Related Proteins/metabolism
مستخلص: The obvious degeneration of articular cartilage occurs in the late stage of osteonecrosis of the femoral head (ONFH), which aggravates the condition of ONFH. This study aimed to demonstrate aberrant activation of autophagy processes in ONFH chondrocytes through bioinformatics and to predict and identify relevant hub genes and pathways. Differentially expressed genes (DEGs) were identified using R software in the GSE74089 dataset from the GEO database. DEGs were crossed with the Human Autophagy Database (HADb) autophagy genes to screen out autophagy-related differential genes (AT-DEGs). GSEA, GSVA, GO, and KEGG pathway enrichment analyses of AT-DEGs were performed. The STRING database was used to analyze the protein-protein interaction (PPI) of the AT-DEGs network, and the MCODE and CytoHubba plugin in the Cytoscape software was used to analyze the key gene cluster module and screen the hub genes. The PPI network of hub genes was constructed using the GeneMANIA database, and functional enrichment and gene connectivity categories were analyzed. The expression levels of hub genes of related genes in the ONFH patients were verified in the dataset GSE123568, and the protein expression was verified by immunohistochemistry in tissues. The analysis of DEGs revealed abnormal autophagy in ONFH cartilage. AT-DEGs in ONFH have special enrichment in macroautophagy, autophagosome membrane, and phosphatidylinositol-3-phosphate binding. In the GSE123568 dataset, it was also found that ATG2B, ATG4B, and UVRAG were all significantly upregulated in ONFH patients. By immunohistochemistry, it was verified that ATG2B, ATG4B, and UVRAG were significantly overexpressed. These three genes regulate the occurrence and extension of autophagosomes through the PI3KC3C pathway. Finally, we determined that chondrocytes in ONFH undergo positive regulation of autophagy through the corresponding pathways involved in three genes: ATG2B, ATG4B, and UVRAG.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
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فهرسة مساهمة: Keywords: Autophagy; Autophagy-related genes; Bioinformatics; Chondrocytes; Osteonecrosis of femoral head
المشرفين على المادة: 0 (Autophagy-Related Proteins)
تواريخ الأحداث: Date Created: 20240517 Date Completed: 20240807 Latest Revision: 20240903
رمز التحديث: 20240903
DOI: 10.1007/s10735-024-10200-w
PMID: 38758521
قاعدة البيانات: MEDLINE
الوصف
تدمد:1567-2387
DOI:10.1007/s10735-024-10200-w