A role of TRIM59 in pulmonary hypertension: modulating the protein ubiquitylation modification.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37978515", "kind": "science-record", "revision": 4, "content_hash": "sha256:af417ca7d20b91e3e4d8bd402ff22ef0fbba36279c77a29605ce5ef4e050ff98", "created_at": "2026-11-01T19:02:53Z", "updated_at": "2026-11-01T22:53:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A role of TRIM59 in pulmonary hypertension: modulating the protein ubiquitylation modification.", "doi": "10.1186/s12967-023-04712-4", "pmid": "37978515", "authors": ["Yingli Liu", "Li Zhu", "Yue Ming", "Zhuhua Wu", "Lili Zhang", "Qi Chen", "Yong Qi"], "journal": "Journal of translational medicine", "year": 2023, "abstract": "BACKGROUND: Pulmonary hypertension (PH), an infrequent disease, is characterized by excessive pulmonary vascular remodeling and proliferation of pulmonary artery smooth muscle cells (PASMCs). However, its underlying molecular mechanisms remain unclear. Uncovering its molecular mechanisms will be beneficial to the treatment of PH.\nMETHODS: Differently expressed genes (DEGs) in the lung tissues of PH patients were analyzed with a GEO dataset GSE113439. From these DEGs, we focused on TRIM59 which was highly expressed in PH patients. Subsequently, the expression of TRIM59 in the pulmonary arteries of PH patients, lung tissues of PH rat model and PASMCs cultured in a hypoxic condition was verified by quantitative real-time PCR (qPCR), western blot and immunohistochemistry. Furthermore, the role of TRIM59 in PAMSC proliferation and pathological changes in PH rats was assessed via gain-of-function and loss-of-function experiments. In addition, the transcriptional regulation of YAP1/TEAD4 on TRIM59 was confirmed by qPCR, western blot, luciferase reporter assay, ChIP and DNA pull-down. In order to uncover the underlying mechanisms of TRIM59, a protein ubiquitomics and a CoIP- HPLC-MS/MS were companied to identify the direct targets of TRIM59.\nRESULTS: TRIM59 was highly expressed in the pulmonary arteries of PH patients and lung tissues of PH rats. Over-expression of TRIM59 accelerated the proliferation of PASMCs, while TRIM59 silencing resulted in the opposite results. Moreover, TRIM59 silencing mitigated the injuries in heart and lung and attenuated pulmonary vascular remodeling during PH. In addition, its transcription was positively regulated by YAP1/TEAD4. Then we further explored the underlying mechanisms of TRIM59 and found that TRIM59 overexpression resulted in an altered ubiquitylation of proteins. Accompanied with the results of CoIP- HPLC-MS/MS, 34 proteins were identified as the direct targets of TRIM59.\nCONCLUSION: TRIM59 was highly expressed in PH patients and promoted the proliferation of PASMCs and pulmonary vascular remodeling, thus contributing to the pathogenesis of PH. It is indicated that TRIM59 may become a potential target for PH treatment.", "claims": [{"id": "claim-method", "statement": "Differences among groups were analyzed using Student’s t test or 1-way ANOVA followed by Tukey’s multiple comparison as the post hoc test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37978515", "locator": "sections[20] \"Statistical analysis\" paragraph 2", "quote": "Differences among groups were analyzed using Student’s t test or 1-way ANOVA followed by Tukey’s multiple comparison as the post hoc test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37978515", "locator": "sections[32] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "TRIM59 was highly expressed in PH patients and promoted the proliferation of PASMCs and pulmonary vascular remodeling, thus contributing to the pathogenesis of PH.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37978515", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "TRIM59 was highly expressed in PH patients and promoted the proliferation of PASMCs and pulmonary vascular remodeling, thus contributing to the pathogenesis of PH."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "TRIM59 was highly expressed in PH patients and promoted the proliferation of PASMCs and pulmonary vascular remodeling, thus contributing to the pathogenesis of PH.", "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:37978515"], "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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Over-expression of TRIM59 accelerated the p", "tal animals Six-week-old male Sprague Dawley rats were obtained from Liaoning Changsheng Biotechnol"], "order_basis": "paper_text_order:688", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nts, lung tissues of PH rat model and PASMCs cultured in a hypoxic condition was verified by quantita", "arved in serum-free medium for 3 h, and then cultured in a normoxic condition (21% O2, 5% CO2) or a h", "Biotechnology Co., Ltd (Shanghai, China) and cultured in DMEM medium (Servicebio Technology Co., Ltd,", "from iCell Bioscience (Shanghai, China) and cultured in iCell primary smooth muscle cell low serum c"], "order_basis": "paper_text_order:708", "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": ["was verified by quantitative real-time PCR (qPCR), western blot and immunohistochemistry. Fur", "ion of YAP1/TEAD4 on TRIM59 was confirmed by qPCR, western blot, luciferase reporter assay, Ch", "poxic condition was verified by quantitative real-time PCR (qPCR), western blot and immunohistochemistr", "ery tissues from PH patients was verified by qPCR and western blot (Fig. 1B, C). Also, immunoh"], "order_basis": "paper_text_order:769", "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": ["rified by quantitative real-time PCR (qPCR), western blot and immunohistochemistry. Furthermore, the r", "YAP1/TEAD4 on TRIM59 was confirmed by qPCR, western blot, luciferase reporter assay, ChIP and DNA pul", "es from PH patients was verified by qPCR and western blot (Fig. 1B, C). Also, immunohistochemistry sta", "gh expression of TRIM59 revealed by qPCR and western blot in this study, and data from GSE113439. Thes"], "order_basis": "paper_text_order:791", "id": "assay:4"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ative real-time PCR (qPCR), western blot and immunohistochemistry. Furthermore, the role of TRIM59 in PAMSC pr", "by qPCR and western blot (Fig. 1B, C). Also, immunohistochemistry staining showed a high TRIM59 level in the p", "PH patients was detected by western blot. 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