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pmid:33777519

Identification of fibroblast activation-related genes in two acute kidney injury models.

Weiming Deng · Xiangling Wei · Zhanwen Dong · Jinhua Zhang · Zhengyu Huang · Ning Na

PeerJ · 2021 doi:10.7717/peerj.10926

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

absent

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title
Identification of fibroblast activation-related genes in two acute kidney injury models.
doi
10.7717/peerj.10926
pmid
33777519
authors array · 6 items
[0]
Weiming Deng
[1]
Xiangling Wei
[2]
Zhanwen Dong
[3]
Jinhua Zhang
[4]
Zhengyu Huang
[5]
Ning Na
journal
PeerJ
year
2021
abstract
BACKGROUND: Ischemia-reperfusion injury and drug-induced nephrotoxicity are the two most common reasons for acute kidney injury (AKI). However, little attention has been paid to early activation of fibroblasts in the progression of AKI to chronic kidney disease (CKD). The present study aimed to identify related genes and pathways on fibroblast activation in two mouse models of AKI: ischemia-reperfusion injury (IRI) model and folic acid (FA)-induced injury model. METHODS: The microarray expression profiles of GSE62732 and GSE121190 were downloaded from the GEO database, and the differentially expressed genes (DEGs) was analyzed using the Limma package of R software. Principal component analysis (PCA) was also performed using R. The functional information of gene products was annotated by Gene Ontology (GO) and DAVID online database, and the pathway analysis was carried out by using the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) database. Protein-protein interactions (PPI) network was constructed by STRING and Cytoscape. Furthermore, in the Hypoxia/Reoxygenation (H/R) model, the morphological changes of cells were observed under microscope and the expression of the hub genes in NRK-49F cells were validated by qRT-PCR assays. RESULTS: A total of 457 DEGs were identified. Among these, 215 DEGs were upregulated and 242 DEGs were downregulated in the acute injured samples compared with uninjured samples. The GO enrichment analysis indicated that these DEGs were mainly involved in transport, the oxidation-reduction process, the metabolic process, metal ion binding, hydrolase activity, and oxidoreductase activity. The KEGG analysis revealed that these DEGs were significantly enriched in the PI3K-Akt signaling pathway, protein digestion and absorption pathway, and focal adhesion pathway. The hub genes including Hnf4α, Pck1 and Timp1 were validated by the qRT-PCR assay in NRK-49F cells in the H/R model. CONCLUSIONS: Hnf4α, Pck1 and Timp-1 may play a pivotal role in the early activation of fibroblasts, providing novel therapeutic strategies for early prediction and treatment of renal fibrosis.
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Expression Profiling of Fibroblasts in Chronic and Acute Disease Models
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Gene Expression Profiling of Fibroblasts in Actute Kidney Injury
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and pathways on fibroblast activation in two mouse models of AKI: ischemia-reperfusion injury (
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33777519", "kind": "science-record", "revision": 7, "content_hash": "sha256:6fad6f77a0f0942ed0ac29063ddc6bfad8f8e46f0c069b22e65500f382160dcb", "created_at": "2026-11-01T15:41:30Z", "updated_at": "2026-11-01T22:03:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of fibroblast activation-related genes in two acute kidney injury models.", "doi": "10.7717/peerj.10926", "pmid": "33777519", "authors": ["Weiming Deng", "Xiangling Wei", "Zhanwen Dong", "Jinhua Zhang", "Zhengyu Huang", "Ning Na"], "journal": "PeerJ", "year": 2021, "abstract": "BACKGROUND: Ischemia-reperfusion injury and drug-induced nephrotoxicity are the two most common reasons for acute kidney injury (AKI). However, little attention has been paid to early activation of fibroblasts in the progression of AKI to chronic kidney disease (CKD). The present study aimed to identify related genes and pathways on fibroblast activation in two mouse models of AKI: ischemia-reperfusion injury (IRI) model and folic acid (FA)-induced injury model.\nMETHODS: The microarray expression profiles of GSE62732 and GSE121190 were downloaded from the GEO database, and the differentially expressed genes (DEGs) was analyzed using the Limma package of R software. Principal component analysis (PCA) was also performed using R. The functional information of gene products was annotated by Gene Ontology (GO) and DAVID online database, and the pathway analysis was carried out by using the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) database. Protein-protein interactions (PPI) network was constructed by STRING and Cytoscape. Furthermore, in the Hypoxia/Reoxygenation (H/R) model, the morphological changes of cells were observed under microscope and the expression of the hub genes in NRK-49F cells were validated by qRT-PCR assays.\nRESULTS: A total of 457 DEGs were identified. Among these, 215 DEGs were upregulated and 242 DEGs were downregulated in the acute injured samples compared with uninjured samples. The GO enrichment analysis indicated that these DEGs were mainly involved in transport, the oxidation-reduction process, the metabolic process, metal ion binding, hydrolase activity, and oxidoreductase activity. The KEGG analysis revealed that these DEGs were significantly enriched in the PI3K-Akt signaling pathway, protein digestion and absorption pathway, and focal adhesion pathway. The hub genes including Hnf4α, Pck1 and Timp1 were validated by the qRT-PCR assay in NRK-49F cells in the H/R model.\nCONCLUSIONS: Hnf4α, Pck1 and Timp-1 may play a pivotal role in the early activation of fibroblasts, providing novel therapeutic strategies for early prediction and treatment of renal fibrosis.", "claims": [{"id": "claim-method", "statement": "The differences of cell count in captured pictures and the qRT-PCR results were analyzed by Student’s t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33777519", "locator": "sections[10] \"Statistical analysis\" paragraph 2", "quote": "The differences of cell count in captured pictures and the qRT-PCR results were analyzed by Student’s t-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data are available at NCBI GEO: GSE62732, GSE121190.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33777519", "locator": "sections[25] \"Data Availability\" paragraph 2", "quote": "Data are available at NCBI GEO: GSE62732, GSE121190."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:33777519"], "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:GSE121190"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "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:GSE121190"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33777519", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.10926", 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"access_statement_verbatim": "Data are available at NCBI GEO: GSE62732, GSE121190.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3427561", "GSM3427562", "GSM3427563", "GSM3427564", "GSM3427565", "GSM3427566", "GSM3427567", "GSM3427568", "GSM3427569", "GSM3427570", "GSM3427571", "GSM3427572", "GSM3427573", "GSM3427574", "GSM3427575"], "sample_count": 15, "group_sizes": null, "group_sizes_basis": null, "platform": "11180", "taxon": "Mus musculus", "title": "Expression Profiling of Fibroblasts in Chronic and Acute Disease Models", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE62732", "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=GSE62732", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE62732", "version": null, "note": "Data are available at NCBI GEO: GSE62732, GSE121190.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data are available at NCBI GEO: GSE62732, GSE121190.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1532545", "GSM1532546", "GSM1532547", "GSM1532548", "GSM1532549", "GSM1532550", "GSM1532551", "GSM1532552"], "sample_count": 8, "group_sizes": null, "group_sizes_basis": null, "platform": "1261", "taxon": "Mus musculus", "title": "Gene Expression Profiling of Fibroblasts in Actute Kidney Injury", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33777519:1", "role": "table", "format": "jats-table", "media_type": 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