Transcriptomic analysis and laboratory experiments reveal potential critical genes and regulatory mechanisms in sepsis-associated acute kidney injury.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35957725", "kind": "science-record", "revision": 5, "content_hash": "sha256:3e8630e5f3768353a58c163dcfbaddcff28aaff3b55b3decd8dc3426693c8818", "created_at": "2026-11-01T18:15:03Z", "updated_at": "2026-11-01T22:49:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Transcriptomic analysis and laboratory experiments reveal potential critical genes and regulatory mechanisms in sepsis-associated acute kidney injury.", "doi": "10.21037/atm-22-845", "pmid": "35957725", "authors": ["Boyang Liu", "Shengxiang Ao", "Fang Tan", "Wei Ma", "Haoru Liu", "Huaping Liang", "Xia Yang", "Xinjin Chi"], "journal": "Annals of translational medicine", "year": 2022, "abstract": "Background: Sepsis-associated acute kidney injury (SA-AKI) is one of the most frequent and serious complications of sepsis. However, the transcriptional regulatory network of the pathophysiological mechanism of the kidney has not been revealed. This study identified new mechanisms in SA-AKI using bioinformatics analyses and laboratory-based experiments.\nMethods: We performed transcriptomic profiling of mouse kidneys after cecal ligation and puncture (CLP) to mimic clinical sepsis. RNA from kidney samples from the CLP and control groups was isolated and analyzed using bulk messenger RNA (mRNA)-seq. Differentially expressed genes (DEGs) between the two groups were identified, and GO, KEGG and GSEA pathway enrichment analyses were performed. The protein-protein interaction (PPI) network of DEGs and hub genes was analyzed. The hub genes were verified using quantitative real-time polymerase chain reaction (qPCR) or Western blotting. The interaction network, targeted microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) of hub genes were predicted, and the critical miRNA-hub gene regulatory axis was verified using qPCR, Western blotting, malondialdehyde (MDA) determination and flow cytometry. Correlation analyses of N6-adenosine methylation (m6A) RNA methylation regulators and hub genes and m6A modification analysis were performed.\nResults: A total of 4,754 DEGs were identified between the two groups using high-throughput sequencing. The pathways in which DEGs were enriched included ferroptosis (the highest enrichment score), apoptosis, and the PI3K-Akt, NF-kappa B and IL-17 signaling pathways. Seven (Hmox1, Spp1, Socs3, Mapk14, Lcn2, Cxcl1 and Cxcl12) of the 15 hub genes were involved in the KEGG pathway. mmu-miR-7212-5p-Hmox1 was a key RNA regulatory axis in ferroptosis. m6A RNA methylation modifications were involved in SA-AKI. The correlation analyses showed the close interactions among the m6A RNA methylation regulators and important hub genes.\nConclusions: The findings of this study provide new insights into the mechanism regulating the occurrence and progression of SA-AKI. The mmu-miR-7212-5p-Hmox1 axis in ferroptosis and m6A RNA methylation regulators may have potential clinical significance for the future treatment of SA-AKI. The datasets generated for this study can be found in the repository of the GEO database (Series number: GSE186822).", "claims": [{"id": "claim-method", "statement": "Differential expression analysis was performed using the DESeq R package (27).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35957725", "locator": "sections[5] \"RNA sequencing and differentially expressed gene analysis\" paragraph 2", "quote": "Differential expression analysis was performed using the DESeq R package (27)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-22-845/dss", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35957725", "locator": "sections[32] \"Footnotes\" paragraph 2", "quote": "Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-22-845/dss"}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 4,754 DEGs were identified between the two groups using high-throughput sequencing.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35957725", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 4,754 DEGs were identified between the two groups using high-throughput sequencing."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 4,754 DEGs were identified between the two groups using high-throughput sequencing.", "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:35957725"], "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. 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Methods: We performed transcriptomic profiling of mouse kidneys after cecal ligat", "to construct a model of sepsis (24,25). For RNA sequencing, 5 mice were randomly divided into 2 groups:", "P, and the kidneys were taken for subsequent RNA sequencing. Six to eight weeks mice were used for quant"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"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": ["ds: We performed transcriptomic profiling of mouse kidneys after cecal ligation and puncture (C", "except for the ligation and perforation. The mice were sacrificed via neck fracture 6 hours after CLP, and the", ", with a 12-h/12-h light-dark cycle, and the mice were free to eat and drink. According to a common", "del of sepsis (24,25). For RNA sequencing, 5 mice were randomly divided into 2 groups: the CLP grou"], "order_basis": "paper_text_order:512", "id": "assay:2"}, {"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": ["itative real-time polymerase chain reaction (qPCR) or Western blotting. The interaction networ", "-hub gene regulatory axis was verified using qPCR, Western blotting, malondialdehyde (MDA) det", "itative real-time polymerase chain reaction (qPCR) (3 mice per group) and Western blotting (3"], "order_basis": "paper_text_order:1021", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["eal-time polymerase chain reaction (qPCR) or Western blotting. The interaction network, targeted microRNAs", "ene regulatory axis was verified using qPCR, Western blotting, malondialdehyde (MDA) determination and flo", "chain reaction (qPCR) (3 mice per group) and Western blotting (3 mice per group) verification, as describe", "the only difference was that the kidneys for Western blotting analysis were taken 24 hours after CLP/sham"], "order_basis": "paper_text_order:1030", "id": "assay:4"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ing, malondialdehyde (MDA) determination and flow cytometry. Correlation analyses of N6-adenosine methyl"], "order_basis": "paper_text_order:1295", "id": "assay:5"}, {"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": ["ferroptosis (the highest enrichment score), apoptosis, and the PI3K-Akt, NF-kappa B and IL-17 sign"], "order_basis": "paper_text_order:1652", "id": "assay:6"}, {"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": ["Differential expression analysis was performed using the DESeq R package (27)."], "order_basis": "consumes_earlier_output", "id": "assay:7"}]}