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pmid:38329418

Identification of renal ischemia reperfusion injury-characteristic genes, pathways and immunological micro-environment features through bioinformatics approaches.

Xinghua Lv · Qian Fan · Xuanjie Li · Peng Li · Zhanhai Wan · Xuena Han · Hao Wang · Xiaoxia Wang · Lin Wu · Bin Huo · Li Yang · Gen Chen · Yan Zhang

Aging · 2024 doi:10.18632/aging.205471

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Identification of renal ischemia reperfusion injury-characteristic genes, pathways and immunological micro-environment features through bioinformatics approaches.
doi
10.18632/aging.205471
pmid
38329418
authors array · 13 items
[0]
Xinghua Lv
[1]
Qian Fan
[2]
Xuanjie Li
[3]
Peng Li
[4]
Zhanhai Wan
[5]
Xuena Han
[6]
Hao Wang
[7]
Xiaoxia Wang
[8]
Lin Wu
[9]
Bin Huo
[10]
Li Yang
[11]
Gen Chen
[12]
Yan Zhang
journal
Aging
year
2024
abstract
BACKGROUND: Biomarkers and pathways associated with renal ischemia reperfusion injury (IRI) had not been well unveiled. This study was intended to investigate and summarize the regulatory networks for related hub genes. Besides, the immunological micro-environment features were evaluated and the correlations between immune cells and hub genes were also explored. METHODS: GSE98622 containing mouse samples with multiple IRI stages and controls was collected from the GEO database. Differentially expressed genes (DEGs) were recognized by the R package limma, and the GO and KEGG analyses were conducted by DAVID. Gene set variation analysis (GSVA) and weighted gene coexpression network analysis (WGCNA) had been implemented to uncover changed pathways and gene modules related to IRI. Besides the known pathways such as apoptosis pathway, metabolic pathway, and cell cycle pathways, some novel pathways were also discovered to be critical in IRI. A series of novel genes associated with IRI was also dug out. An IRI mouse model was constructed to validate the results. RESULTS: The well-known IRI marker genes (Kim1 and Lcn2) and novel hub genes (Hbegf, Serpine2, Apbb1ip, Trip13, Atf3, and Ncaph) had been proved by the quantitative real-time polymerase chain reaction (qRT-PCR). Thereafter, miRNAs targeted to the dysregulated genes were predicted and the miRNA-target network was constructed. Furthermore, the immune infiltration for these samples was predicted and the results showed that macrophages infiltrated to the injured kidney to affect the tissue repair or fibrosis. Hub genes were significantly positively or negatively correlated with the macrophage abundance indicating they played a crucial role in macrophage infiltration. CONCLUSIONS: Consequently, the pathways, hub genes, miRNAs, and the immune microenvironment may explain the mechanism of IRI and might be the potential targets for IRI treatments.
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The well-known IRI marker genes (Kim1 and Lcn2) and novel hub genes (Hbegf, Serpine2, Apbb1ip, Trip13, Atf3, and Ncaph) had been proved by the quantitative real-time polymerase chain reaction (qRT-PCR).
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Thereafter, miRNAs targeted to the dysregulated genes were predicted and the miRNA-target network was constructed.
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Hub genes were significantly positively or negatively correlated with the macrophage abundance indicating they played a crucial role in macrophage infiltration.
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Transcriptome profile of a murine renal bilateral ischemia reperfusion model 2 hours to 12 months post injury
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associated with IRI was also dug out. An IRI mouse model was constructed to validate the results. RES
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associated with IRI was also dug out. An IRI mouse model was constructed to validate the result
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ental animals Twelve 7-week-old male C57BL/6 mice were subdivided into the sham group (S group, n=3
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also explored. METHODS: GSE98622 containing mouse samples with multiple IRI stages and control
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d to IRI. Besides the known pathways such as apoptosis pathway, metabolic pathway, and cell cycle p
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38329418", "kind": "science-record", "revision": 4, "content_hash": "sha256:460242b0b2fcf8f66934e41b10e18e4cf2a37d8ddc51a45119ce8a6feacd703f", "created_at": "2026-11-01T19:20:16Z", "updated_at": "2026-11-01T22:53:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of renal ischemia reperfusion injury-characteristic genes, pathways and immunological micro-environment features through bioinformatics approaches.", "doi": "10.18632/aging.205471", "pmid": "38329418", "authors": ["Xinghua Lv", "Qian Fan", "Xuanjie Li", "Peng Li", "Zhanhai Wan", "Xuena Han", "Hao Wang", "Xiaoxia Wang", "Lin Wu", "Bin Huo", "Li Yang", "Gen Chen", "Yan Zhang"], "journal": "Aging", "year": 2024, "abstract": "BACKGROUND: Biomarkers and pathways associated with renal ischemia reperfusion injury (IRI) had not been well unveiled. This study was intended to investigate and summarize the regulatory networks for related hub genes. Besides, the immunological micro-environment features were evaluated and the correlations between immune cells and hub genes were also explored.\nMETHODS: GSE98622 containing mouse samples with multiple IRI stages and controls was collected from the GEO database. Differentially expressed genes (DEGs) were recognized by the R package limma, and the GO and KEGG analyses were conducted by DAVID. Gene set variation analysis (GSVA) and weighted gene coexpression network analysis (WGCNA) had been implemented to uncover changed pathways and gene modules related to IRI. Besides the known pathways such as apoptosis pathway, metabolic pathway, and cell cycle pathways, some novel pathways were also discovered to be critical in IRI. A series of novel genes associated with IRI was also dug out. An IRI mouse model was constructed to validate the results.\nRESULTS: The well-known IRI marker genes (Kim1 and Lcn2) and novel hub genes (Hbegf, Serpine2, Apbb1ip, Trip13, Atf3, and Ncaph) had been proved by the quantitative real-time polymerase chain reaction (qRT-PCR). Thereafter, miRNAs targeted to the dysregulated genes were predicted and the miRNA-target network was constructed. Furthermore, the immune infiltration for these samples was predicted and the results showed that macrophages infiltrated to the injured kidney to affect the tissue repair or fibrosis. Hub genes were significantly positively or negatively correlated with the macrophage abundance indicating they played a crucial role in macrophage infiltration.\nCONCLUSIONS: Consequently, the pathways, hub genes, miRNAs, and the immune microenvironment may explain the mechanism of IRI and might be the potential targets for IRI treatments.", "claims": [{"id": "claim-method", "statement": "Limma package [14] was performed to identify DEGs for the IRI stage vs. the control group for GSE98622 after transforming the FPKM to TPM.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38329418", "locator": "sections[4] \"Screening of DEGs\" paragraph 2", "quote": "Limma package [14] was performed to identify DEGs for the IRI stage vs. the control group for GSE98622 after transforming the FPKM to TPM."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The IRI RNA-Seq data and the corresponding clinical data were collected from the GEO database with accession numbers GSE98622, GSE182793, and GSE139107 (Table 1). The analyses were based on GSE98622 which included six controls and 21 disease samples with seven different IRI stages.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38329418", "locator": "sections[3] \"Data collection\" paragraph 2", "quote": "The IRI RNA-Seq data and the corresponding clinical data were collected from the GEO database with accession numbers GSE98622, GSE182793, and GSE139107 (Table 1). The analyses were based on GSE98622 which included six controls and 21 disease samples with seven different IRI stages."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified known and novel hub genes associated with renal IRI, validated them by qRT-PCR, predicted their targeting miRNAs, and linked the hub genes to macrophage infiltration.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38329418", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The well-known IRI marker genes (Kim1 and Lcn2) and novel hub genes (Hbegf, Serpine2, Apbb1ip, Trip13, Atf3, and Ncaph) had been proved by the quantitative real-time polymerase chain reaction (qRT-PCR)."}, {"asset": "source:pmid:38329418", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Thereafter, miRNAs targeted to the dysregulated genes were predicted and the miRNA-target network was constructed."}, {"asset": "source:pmid:38329418", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Hub genes were significantly positively or negatively correlated with the macrophage abundance indicating they played a crucial role in macrophage infiltration."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified known and novel hub genes associated with renal IRI, validated them by qRT-PCR, predicted their targeting miRNAs, and linked the hub genes to macrophage infiltration.", "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:38329418"], "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:GSE139107"], "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:GSE139107"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38329418", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.18632/aging.205471", "sha256": "sha256:78ac68ef516efe335f500aa207a1537381b83daf2dec305a84e6f593c8d9ea80", "bytes": 28214, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.18632/aging.205471", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10911371", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE139107", "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=GSE139107", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE139107", "version": null, "note": "The IRI RNA-Seq data and the corresponding clinical data were collected from the GEO database with accession numbers GSE98622, GSE182793, and GSE139107 (Table 1). 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The analyses were based on GSE98622 which included six controls and 21 disease samples with seven different IRI stages.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The IRI RNA-Seq data and the corresponding clinical data were collected from the GEO database with accession numbers GSE98622, GSE182793, and GSE139107 (Table 1). 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The analyses were based on GSE98622 which included six controls and 21 disease samples with seven different IRI stages.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The IRI RNA-Seq data and the corresponding clinical data were collected from the GEO database with accession numbers GSE98622, GSE182793, and GSE139107 (Table 1). 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE98622", "GSE182793", "GSE139107"], "resolved_accessions": ["GSE98622", "GSE182793", "GSE139107"], "statements": ["The IRI RNA-Seq data and the corresponding clinical data were collected from the GEO database with accession numbers GSE98622, GSE182793, and GSE139107 (Table 1). The analyses were based on GSE98622 which included six controls and 21 disease samples with seven different IRI stages."], "basis": "The paper names GSE98622, GSE182793, GSE139107 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:38329418", "data:geo:GSE139107"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE139107"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:07:59Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 8365, "completion_tokens": 1467, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:38329418", "type": "paper", "label": "pmid:38329418"}, {"id": "source:pmid:38329418", "type": "manuscript", "label": "PMID 38329418 full text"}, {"id": "data:geo:GSE139107", "type": "dataset", "label": "GEO GSE139107"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38329418", "type": "paper", "label": "pmid:38329418"}, {"id": "source:pmid:38329418", "type": "manuscript", "label": "PMID 38329418 full text"}, {"id": "data:geo:GSE139107", "type": "dataset", "label": "GEO GSE139107"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38329418", "type": "extraction", "used": ["source:pmid:38329418"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE139107", "type": "accession_resolution", "used": ["data:geo:GSE139107"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:38329418", "parent_hash": "sha256:3e9a4c75efa6cf1612c2ba518132a314fa995b1bfee624c28eef5436d512d7f5", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE139107 licence not read", "asset:data:geo:GSE139107 not downloaded", "asset:data:geo:GSE182793 licence not read", "asset:data:geo:GSE182793 not downloaded", "asset:data:geo:GSE98622 licence not read", "asset:data:geo:GSE98622 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["associated with IRI was also dug out. An IRI mouse model was constructed to validate the results. RES", "associated with IRI was also dug out. An IRI mouse model was constructed to validate the result", "ental animals Twelve 7-week-old male C57BL/6 mice were subdivided into the sham group (S group, n=3", "also explored. METHODS: GSE98622 containing mouse samples with multiple IRI stages and control"], "order_basis": "paper_text_order:513", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["d to IRI. Besides the known pathways such as apoptosis pathway, metabolic pathway, and cell cycle p"], "order_basis": "paper_text_order:941", "id": "assay:2"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Limma package [14] was performed to identify DEGs for the IRI stage vs. the control group for GSE98622 after transforming the FPKM to TPM."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}