Tilianin Reduces Apoptosis via the ERK/EGR1/BCL2L1 Pathway in Ischemia/Reperfusion-Induced Acute Kidney Injury Mice.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35721209", "kind": "science-record", "revision": 5, "content_hash": "sha256:51f49ed7f52c9c18682e93b20c677b8ccbc06c17dd562ecc8401bbdb7992416f", "created_at": "2026-11-01T18:14:43Z", "updated_at": "2026-11-01T22:49:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Tilianin Reduces Apoptosis via the ERK/EGR1/BCL2L1 Pathway in Ischemia/Reperfusion-Induced Acute Kidney Injury Mice.", "doi": "10.3389/fphar.2022.862584", "pmid": "35721209", "authors": ["Zengying Liu", "Chen Guan", "Chenyu Li", "Ningxin Zhang", "Chengyu Yang", "Lingyu Xu", "Bin Zhou", "Long Zhao", "Hong Luan", "Xiaofei Man", "Yan Xu"], "journal": "Frontiers in pharmacology", "year": 2022, "abstract": "Background: Acute kidney injury (AKI) is a common syndrome impacting about 13.3 million patients per year. Tilianin has been reported to alleviate myocardial ischemia/reperfusion (I/R) injury, while its effect on AKI is unknown; thus, this study aimed to explore if tilianin protects I/R-induced AKI and the underlying mechanisms. Methods: The microarray dataset GSE52004 was downloaded from GEO DataSets (Gene Expression Omnibus). Differential expression analysis and gene-set enrichment analysis (GSEA) were performed by R software to identify apoptosis pathway-related genes. Then, RcisTarget was applied to identify the transcription factor (TF) related to apoptosis. The STRING database was used to construct a protein-protein interaction (PPI) network. Cytoscape software visualized PPI networks, and hub TFs were selected via cytoHubba. AutoDock was used for molecular docking of tilianin and hub gene-encoded proteins. The expression levels of hub genes were assayed and visualized by quantitative real-time PCR, Western blotting, and immunohistochemistry by establishing I/R-induced AKI mouse models. Results: Bioinformatics analysis showed that 34 genes, including FOS, ATF4, and Gadd45g, were involved in the apoptosis pathway. In total, seven hub TFs might play important roles in tilianin-regulating apoptosis pathways. In in vivo, tilianin improved kidney function and reduced the number of TUNEL-positive renal tubular epithelial cells (RTECs) after I/R-induced AKI. Tilianin reduced the activation of the ERK pathway and then downregulated the expression of EGR1. This further ameliorated the expression of anti-apoptotic genes such as BCL2L1 and BCL2, reduced pro-apoptotic genes such as BAD, BAX, and caspase-3, and reduced the release of cytochrome c. Conclusion: Tilianin reduced apoptosis after I/R-induced AKI by the ERK/EGR1/BCL2L1 pathway. Our findings provided novel insights for the first time into the protective effect and underlying molecular mechanisms of tilianin on I/R-induced AKI.", "claims": [{"id": "claim-method", "statement": "Statistical significance was analyzed using ANOVA followed by the Bonferroni post hoc test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35721209", "locator": "sections[14] \"Statistical Analysis\" paragraph 2", "quote": "Statistical significance was analyzed using ANOVA followed by the Bonferroni post hoc test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. These data can be found at: GEO DataSets (Gene Expression Omnibus) GSE52004.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35721209", "locator": "sections[23] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. 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In in vivo, tilianin improved kidney function and reduc", "stochemistry by establishing I/R-induced AKI mouse models. Results: Bioinformatics analysis sho", "parotomy. After the reperfusion of 24 h, the mice were sacrificed. The blood samples were collected to detect", "Materials Animals and Treatment Male C57BL/6 mice were purchased from Jinan Pengyue Experimental An"], "order_basis": "paper_text_order:1168", "id": "assay:6"}, {"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 significance was analyzed using ANOVA followed by the Bonferroni post hoc test."], "order_basis": "consumes_earlier_output", "id": "assay:7"}]}