Cathepsin G promotes arteriovenous fistula maturation by positively regulating the MMP2/MMP9 pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38362707", "kind": "science-record", "revision": 4, "content_hash": "sha256:71c351c53a3e8c336c4c51634cd5197f44ac401598a4d524852763f5acf50899", "created_at": "2026-11-01T19:20:18Z", "updated_at": "2026-11-01T22:53:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Cathepsin G promotes arteriovenous fistula maturation by positively regulating the MMP2/MMP9 pathway.", "doi": "10.1080/0886022X.2024.2316269", "pmid": "38362707", "authors": ["Lemei Hu", "Changqing Zheng", "Ying Kong", "Zhiqing Luo", "Fengzhang Huang", "Zhigang Zhu", "Quhuan Li", "Ming Liang"], "journal": "Renal failure", "year": 2024, "abstract": "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.\nMETHODS 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.\nCONCLUSIONS: 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.", "claims": [{"id": "claim-method", "statement": "Statistical tests included the two-sided unpaired Student’s t-test and two-way ANOVA; p < 0.05 was considered statistically significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38362707", "locator": "sections[10] \"Statistics\" paragraph 2", "quote": "Statistical tests included the two-sided unpaired Student’s t-test and two-way ANOVA; p < 0.05 was considered statistically significant."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38362707", "locator": "sections[26] \"Data availability statement\" paragraph 2", "quote": "All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "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.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38362707", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "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.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38362707"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE119296"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE119296"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38362707", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1080/0886022X.2024.2316269", "sha256": "sha256:dbbf61b4874fb52331c732f77e7cd81454d9fe1883139ad515b59b70a18165b2", "bytes": 43846, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1080/0886022X.2024.2316269", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10878333", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE119296", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119296", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE119296", "version": null, "note": "All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3369535", "GSM3369536", "GSM3369537", "GSM3369538", "GSM3369539", "GSM3369540", "GSM3369541", "GSM3369542", "GSM3369543", "GSM3369544", "GSM3369545", "GSM3369546", "GSM3369547", "GSM3369548", "GSM3369549", "GSM3369550", "GSM3369551", "GSM3369552", "GSM3369553", "GSM3369554", "GSM3369555", "GSM3369556", "GSM3369557", "GSM3369558", "GSM3369559", "GSM3369560", "GSM3369561", "GSM3369562", "GSM3369563", "GSM3369564", "GSM3369565", "GSM3369566", "GSM3369567", "GSM3369568", "GSM3369569", "GSM3369570", "GSM3369571", "GSM3369572"], "sample_count": 38, "group_sizes": null, "group_sizes_basis": null, "platform": "18573", "taxon": "Homo sapiens", "title": "Whole genome transcriptomics of pre-access veins and hemodialysis arteriovenous fistula (AVF) samples from two-stage AVF patients with different maturation outcomes (matured vs. failed)", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE220796", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE220796", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE220796", "version": null, "note": "All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analyzed during this study are included in this article. 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The IHC results demonstrated a sig", "to the mature samples. The results of double-immunofluorescence staining revealed that CTSG was expressed in", "pression of CTSG using immunohistochemistry (IHC) and double-immunofluorescence staining. The"], "order_basis": "paper_text_order:1313", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["e and embedded in paraffin. Cell culture and transfection Vascular smooth muscle cells (VSMCs) were cu", "n plasmid or corresponding empty plasmid was transfected using Lipofectamine 3000, according to the m", "laced, and the cells were cultured for 24 h. Transfection efficiency was measured by real-time quantit", "l-time quantitative PCR (RT-qPCR; 24 h after transfection) and western blotting (48 h after transfecti"], "order_basis": "paper_text_order:3317", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["on Vascular smooth muscle cells (VSMCs) were cultured in a cell culture medium supplemented with 2% F", "on Vascular smooth muscle cells (VSMCs) were cultured in a cell culture medium supplemented with 2"], "order_basis": "paper_text_order:3372", "id": "assay:3"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["was measured by real-time quantitative PCR (RT-qPCR; 24 h after transfection) and western blotti", "s measured by real-time quantitative PCR (RT-qPCR; 24 h after transfection) and western blotti", "4 h. Transfection efficiency was measured by real-time quantitative PCR (RT-qPCR; 24 h after transfection) and weste"], "order_basis": "paper_text_order:4069", "id": "assay:4"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["e PCR (RT-qPCR; 24 h after transfection) and western blotting (48 h after transfection). Supplementary Mat"], "order_basis": "paper_text_order:4135", "id": "assay:5"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Statistical tests included the two-sided unpaired Student’s t-test and two-way ANOVA; p < 0.05 was considered statistically significant."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}