Cathepsin G promotes arteriovenous fistula maturation by positively regulating the MMP2/MMP9 pathway
Background Arteriovenous fistula (AVF) is currently the preferred vascular access for hemodialysis patients. However, the low maturation rate of AVF severely affects its use in patients. A more comprehensive understanding and study of the mechanisms of AVF maturation is urgently needed.Methods and r...
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| Format: | Article |
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2316269 |
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| author | Lemei Hu Changqing Zheng Ying Kong Zhiqing Luo Fengzhang Huang Zhigang Zhu Quhuan Li Ming Liang |
| author_facet | Lemei Hu Changqing Zheng Ying Kong Zhiqing Luo Fengzhang Huang Zhigang Zhu Quhuan Li Ming Liang |
| author_sort | Lemei Hu |
| collection | DOAJ |
| description | Background Arteriovenous fistula (AVF) is currently the preferred vascular access for hemodialysis patients. However, the low maturation rate of AVF severely affects its use in patients. A more comprehensive understanding and study of the mechanisms of AVF maturation is urgently needed.Methods and results In this study, we downloaded the publicly available datasets (GSE119296 and GSE220796) from the Gene Expression Omnibus (GEO) and merged them for subsequent analysis. We screened 84 differentially expressed genes (DEGs) and performed the functional enrichment analysis. Next, we integrated the results obtained from the degree algorithm provided by the Cytohubba plug-in, Molecular complex detection (MCODE) plug-in, weighted gene correlation network analysis (WGCNA), and Least absolute shrinkage and selection operator (LASSO) logistic regression. This integration allowed us to identify CTSG as a hub gene associated with AVF maturation. Through the literature search and Pearson’s correlation analysis, the genes matrix metalloproteinase 2 (MMP2) and MMP9 were identified as potential downstream effectors of CTSG. We then collected three immature clinical AVF vein samples and three mature samples and validated the expression of CTSG using immunohistochemistry (IHC) and double-immunofluorescence staining. The IHC results demonstrated a significant decrease in CTSG expression levels in the immature AVF vein samples compared to the mature samples. The results of double-immunofluorescence staining revealed that CTSG was expressed in both the intima and media of AVF veins. Moreover, the expression of CTSG in vascular smooth muscle cells (VSMCs) was significantly higher in the mature samples compared to the immature samples. The results of Masson’s trichrome and collagen I IHC staining demonstrated a higher extent of collagen deposition in the media of immature AVF veins compared to the mature. By constructing an in vitro CTSG overexpression model in VSMCs, we found that CTSG upregulated the expression of MMP2 and MMP9 while downregulating the expression of collagen I and collagen III. Furthermore, CTSG was found to inhibit VSMC migration.Conclusions CTSG may promote AVF maturation by stimulating the secretion of MMP2 and MMP9 from VSMCs and reducing the extent of medial fibrosis in AVF veins by inhibiting the secretion of collagen I and collagen III. |
| format | Article |
| id | doaj-art-025ce9eaeae0475ead26f6e732a106c5 |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-025ce9eaeae0475ead26f6e732a106c52025-01-23T04:17:47ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2316269Cathepsin G promotes arteriovenous fistula maturation by positively regulating the MMP2/MMP9 pathwayLemei Hu0Changqing Zheng1Ying Kong2Zhiqing Luo3Fengzhang Huang4Zhigang Zhu5Quhuan Li6Ming Liang7Department of Nephrology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, PR ChinaSchool of Biology and Biological Engineering, South China University of Technology, Guangzhou, PRChinaSchool of Biology and Biological Engineering, South China University of Technology, Guangzhou, PRChinaSchool of Biology and Biological Engineering, South China University of Technology, Guangzhou, PRChinaDepartment of Nephrology, Guangzhou First People’s Hospital, Guangzhou, PR ChinaDepartment of Geriatrics, Division of Hematology and Oncology, Second Affiliated Hospital, Guangzhou First People’s Hospital, College of Medicine, South China University of Technology, Guangzhou, PR ChinaSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou, PR ChinaDepartment of Nephrology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, PR ChinaBackground Arteriovenous fistula (AVF) is currently the preferred vascular access for hemodialysis patients. However, the low maturation rate of AVF severely affects its use in patients. A more comprehensive understanding and study of the mechanisms of AVF maturation is urgently needed.Methods and results In this study, we downloaded the publicly available datasets (GSE119296 and GSE220796) from the Gene Expression Omnibus (GEO) and merged them for subsequent analysis. We screened 84 differentially expressed genes (DEGs) and performed the functional enrichment analysis. Next, we integrated the results obtained from the degree algorithm provided by the Cytohubba plug-in, Molecular complex detection (MCODE) plug-in, weighted gene correlation network analysis (WGCNA), and Least absolute shrinkage and selection operator (LASSO) logistic regression. This integration allowed us to identify CTSG as a hub gene associated with AVF maturation. Through the literature search and Pearson’s correlation analysis, the genes matrix metalloproteinase 2 (MMP2) and MMP9 were identified as potential downstream effectors of CTSG. We then collected three immature clinical AVF vein samples and three mature samples and validated the expression of CTSG using immunohistochemistry (IHC) and double-immunofluorescence staining. The IHC results demonstrated a significant decrease in CTSG expression levels in the immature AVF vein samples compared to the mature samples. The results of double-immunofluorescence staining revealed that CTSG was expressed in both the intima and media of AVF veins. Moreover, the expression of CTSG in vascular smooth muscle cells (VSMCs) was significantly higher in the mature samples compared to the immature samples. The results of Masson’s trichrome and collagen I IHC staining demonstrated a higher extent of collagen deposition in the media of immature AVF veins compared to the mature. By constructing an in vitro CTSG overexpression model in VSMCs, we found that CTSG upregulated the expression of MMP2 and MMP9 while downregulating the expression of collagen I and collagen III. Furthermore, CTSG was found to inhibit VSMC migration.Conclusions CTSG may promote AVF maturation by stimulating the secretion of MMP2 and MMP9 from VSMCs and reducing the extent of medial fibrosis in AVF veins by inhibiting the secretion of collagen I and collagen III.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2316269Bioinformatic analysisarteriovenous fistulavascular smooth muscle cellsCTSGnon-maturation |
| spellingShingle | Lemei Hu Changqing Zheng Ying Kong Zhiqing Luo Fengzhang Huang Zhigang Zhu Quhuan Li Ming Liang Cathepsin G promotes arteriovenous fistula maturation by positively regulating the MMP2/MMP9 pathway Renal Failure Bioinformatic analysis arteriovenous fistula vascular smooth muscle cells CTSG non-maturation |
| title | Cathepsin G promotes arteriovenous fistula maturation by positively regulating the MMP2/MMP9 pathway |
| title_full | Cathepsin G promotes arteriovenous fistula maturation by positively regulating the MMP2/MMP9 pathway |
| title_fullStr | Cathepsin G promotes arteriovenous fistula maturation by positively regulating the MMP2/MMP9 pathway |
| title_full_unstemmed | Cathepsin G promotes arteriovenous fistula maturation by positively regulating the MMP2/MMP9 pathway |
| title_short | Cathepsin G promotes arteriovenous fistula maturation by positively regulating the MMP2/MMP9 pathway |
| title_sort | cathepsin g promotes arteriovenous fistula maturation by positively regulating the mmp2 mmp9 pathway |
| topic | Bioinformatic analysis arteriovenous fistula vascular smooth muscle cells CTSG non-maturation |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2316269 |
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