Uncovering key molecules and immune landscape in cholestatic liver injury: implications for pathogenesis and drug therapy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37229242", "kind": "science-record", "revision": 4, "content_hash": "sha256:a8ebe4a1b70f41e84b9fe69f44458422f1789f6c070845c510c2f0edc78d98b7", "created_at": "2026-11-01T19:01:56Z", "updated_at": "2026-11-01T22:51:59Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Uncovering key molecules and immune landscape in cholestatic liver injury: implications for pathogenesis and drug therapy.", "doi": "10.3389/fphar.2023.1171512", "pmid": "37229242", "authors": ["Shuailing Song", "Xiao Li", "Chong Geng", "Yaoyu Guo", "Yi Yang", "Chunhui Wang"], "journal": "Frontiers in pharmacology", "year": 2023, "abstract": "Background: Cholestasis is a common pathological process in a variety of liver diseases that may lead to liver fibrosis, cirrhosis, and even liver failure. Cholestasis relief has been regarded as a principal target in the management of multiple chronic cholestasis liver diseases like primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) at present. However, complicated pathogenesis and limited acknowledgments fettered therapeutic development. Therefore, this study aimed to systematically analyze miRNA-mRNA regulatory networks in cholestatic liver injury in order to provide new treatment strategies. Methods: Gene Expression Omnibus (GEO) database (GSE159676) was used to screen differentially expressed hepatic miRNAs and mRNAs in the PSC vs. control comparison and the PBC vs. control comparison, respectively. MiRWalk 2.0 tool was used to predict miRNA-mRNA pairs. Subsequently, functional analysis and immune cell infiltration analysis were performed to explore the pivotal functions of the target genes. RT-PCR was used to verify the result. Results: In total, a miRNA-mRNA network including 6 miRNAs (miR-122, miR-30e, let-7c, miR-107, miR-503, and miR-192) and 8 hub genes (PTPRC, TYROBP, LCP2, RAC2, SYK, TLR2, CD53, and LAPTM5) was constructed in cholestasis. Functional analysis revealed that these genes were mainly involved in the regulation of the immune system. Further analysis revealed that resting memory CD4 T cells and monocytes could potentially participate in cholestatic liver injury. The expressions of DEMis and eight hub genes were verified in ANIT-induced and BDL-induced cholestatic mouse models. Furthermore, SYK was found to have an impact on the response to UDCA, and its mechanism was possibly associated with complement activation and monocyte reduction. Conclusion: In the present study, a miRNA-mRNA regulatory network was constructed in cholestatic liver injury, which mostly mediated immune-related pathways. Moreover, the targeted gene SYK and monocytes were found to be related to UDCA response in PBC.", "claims": [{"id": "claim-method", "statement": "Student’s t-test was carried out to compare two groups, and one-way analysis of variance (ANOVA) was applied for multigroup (≥3) comparisons by SPSS 16.0 (Chicago, United States).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37229242", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "Student’s t-test was carried out to compare two groups, and one-way analysis of variance (ANOVA) was applied for multigroup (≥3) comparisons by SPSS 16.0 (Chicago, United States)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37229242", "locator": "sections[25] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study constructed a cholestasis-associated miRNA-mRNA regulatory network comprising 6 miRNAs and 8 hub genes, with SYK and monocyte infiltration implicated in the response to UDCA.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37229242", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In total, a miRNA-mRNA network including 6 miRNAs (miR-122, miR-30e, let-7c, miR-107, miR-503, and miR-192) and 8 hub genes (PTPRC, TYROBP, LCP2, RAC2, SYK, TLR2, CD53, and LAPTM5) was constructed in cholestasis."}, {"asset": "source:pmid:37229242", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Furthermore, SYK was found to have an impact on the response to UDCA, and its mechanism was possibly associated with complement activation and monocyte reduction."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study constructed a cholestasis-associated miRNA-mRNA regulatory network comprising 6 miRNAs and 8 hub genes, with SYK and monocyte infiltration implicated in the response to UDCA.", "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:37229242"], "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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Furthermore, SYK was found to have a", "given a consistent volume of olive oil. All mice were sacrificed 48 h after treatment. For BDL-induced choles", "was performed after midline laparotomy. All mice were sacrificed 21 days after BDL. Serum and liver samples w", "China). For ANIT-induced cholestasis model, mice were randomly assigned to the control group and t"], "order_basis": "paper_text_order:1716", "id": "assay:1"}, {"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": ["firmed the result (Supplementary Figure S1). RT-qPCR showed that the expression of four DEMis (mi", "Mis/DEMs in ANIT-induced cholestatic mice by RT-qPCR. (A) H&E staining and MPO immunofluorescence", "estatic mice. (A) Hepatic DEMi expression by RT-qPCR; (B) Hepatic hub gene expression by RT-qPCR;", "RT-qPCR; (B) Hepatic hub gene expression by RT-qPCR; (C) Hepatic hub gene expression in GSE16686"], "order_basis": "paper_text_order:4297", "id": "assay:2"}, {"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": ["ssion by ANIT treatment was also detected by western blot (Figure 5E). Furthermore, to better mimic th", "nt (p < 0.05); (E) SYK protein expression by western blot. Triangles represent liver necrosis; arrows"], "order_basis": "paper_text_order:5364", "id": "assay:3"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ic mice by RT-qPCR. 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