Inhibition of Key Glycolytic Enzyme Hexokinase 2 Ameliorates Psoriasiform Inflammation in vitro and in vivo.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37965102", "kind": "science-record", "revision": 2, "content_hash": "sha256:ac73a310a0d4cfec78934b8c4e227184ee5d02e6d66494ec4e6b7c70d361ec82", "created_at": "2026-11-01T19:02:52Z", "updated_at": "2026-11-01T21:31:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Inhibition of Key Glycolytic Enzyme Hexokinase 2 Ameliorates Psoriasiform Inflammation in vitro and in vivo.", "doi": "10.2147/CCID.S435624", "pmid": "37965102", "authors": ["Le Zhuang", "Weiyuan Ma", "Jing Jiao"], "journal": "Clinical, cosmetic and investigational dermatology", "year": 2023, "abstract": "Purpose: Epidermal keratinocytes with an abnormal glucose metabolism have been identified in psoriasis. Hexokinase 2 (HK2) is a crucial enzyme involved in glycolytic metabolic pathways. However, the expression of HK2 and its potential therapeutic effects in psoriasis remains unclear. This study aimed to investigate the expression pattern of HK2 and evaluate its therapeutic effects in psoriasis.\nPatients and Methods: A gene expression dataset (GSE121212) downloaded from the Gene Expression Omnibus (GEO) database was used to examine the expression of HK2 in psoriasis. HK2 RNA and protein expression were investigated in psoriasis vulgaris (n=5) and healthy (n=5) samples. Immunohistochemistry for HK2 was performed on psoriasis vulgaris (n=22) and healthy skin (n=10) samples. Additionally, HaCaT cells were treated with M5 (interleukin [IL]-17A, tumor necrosis factor-α, IL-1α, IL-22, and Oncostatin-M) to induce a psoriatic inflammation cell model. A mouse model of psoriatic inflammation was established using topical 5% imiquimod cream. Psoriasis-like cells and mouse models were treated with the HK2 inhibitor 3-bromopyruvate (3-BrPA). Cell proliferation, glucose consumption, and lactate production were assessed. Furthermore, the activation of nuclear factor-kappa B (NF-Kb) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was investigated using Western blot analysis.\nResults: According to the GEO dataset, HK2 expression was significantly elevated in psoriasis. Upregulation of HK2 in psoriatic tissues was confirmed by quantitative real-time polymerase chain reaction and Western blotting. The immunohistochemistry score for HK2 was higher in psoriatic lesions than in healthy skin. 3-BrPA inhibited the proliferation and glycolysis of M5-stimulated HaCaT cells. Topical 3-BrPA ameliorated imiquimod-induced psoriasis-like dermatitis. Activation of NF-kB and NLRP3 was downregulated by 3-BrPA treatment.\nConclusion: Our study revealed that the glycolytic enzyme HK2 was upregulated in psoriasis and that the HK2 inhibitor 3-BrPA exhibited therapeutic effects in psoriasis cell and mouse models.", "claims": [{"id": "claim-method", "statement": "Statistical significance for categorical data was tested using the two-tailed Fisher’s exact test, while the Mann–Whitney or Kruskal–Wallis tests were performed for continuous data.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37965102", "locator": "sections[11] \"Statistical Analysis\" paragraph 2", "quote": "Statistical significance for categorical data was tested using the two-tailed Fisher’s exact test, while the Mann–Whitney or Kruskal–Wallis tests were performed for continuous data."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data supporting this study’s findings are available by correspondence author Weiyuan Ma upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37965102", "locator": "sections[20] \"Data Sharing Statement\" paragraph 2", "quote": "Data supporting this study’s findings are available by correspondence author Weiyuan Ma upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our study revealed that the glycolytic enzyme HK2 was upregulated in psoriasis and that the HK2 inhibitor 3-BrPA exhibited therapeutic effects in psoriasis cell and mouse models.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37965102", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our study revealed that the glycolytic enzyme HK2 was upregulated in psoriasis and that the HK2 inhibitor 3-BrPA exhibited therapeutic effects in psoriasis cell and mouse models."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our study revealed that the glycolytic enzyme HK2 was upregulated in psoriasis and that the HK2 inhibitor 3-BrPA exhibited therapeutic effects in psoriasis cell and mouse models.", "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:37965102"], "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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A mouse model of psoriatic inflammation was established us", "nduce a psoriatic inflammation cell model. A mouse model of psoriatic inflammation was establis", "5% imiquimod cream. Psoriasis-like cells and mouse models were treated with the HK2 inhibitor 3"], "order_basis": "paper_text_order:55", "id": "assay:1"}, {"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": ["is vulgaris (n=5) and healthy (n=5) samples. Immunohistochemistry for HK2 was performed on psoriasis vulgaris", "ase chain reaction and Western blotting. The immunohistochemistry score for HK2 was higher in psoriatic lesion", "r Western blotting immediately after biopsy. Immunohistochemistry was performed on paraffin-embedded tissue sa"], "order_basis": "paper_text_order:741", "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": ["ted protein 3 (NLRP3) was investigated using Western blot analysis. Results: According to the GEO data", "tive real-time polymerase chain reaction and Western blotting. The immunohistochemistry score for HK2 was", "lthy skin (n = 5) samples were collected for Western blotting immediately after biopsy. Immunohistochemist"], "order_basis": "paper_text_order:1448", "id": "assay:3"}, {"role": "data_generation", "definition_id": "clinical_cohort", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["on paraffin-embedded tissue samples from 22 patients with psoriasis and 10 healthy controls. The diagn", "nd 10 healthy controls. The diagnoses of all patients were confirmed histopathologically. Cell Lines an"], "order_basis": "paper_text_order:2675", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ican Type Culture Collection. The cells were cultured in a humidified environment at 37°C with 5% CO2"], "order_basis": "paper_text_order:2932", "id": "assay:5"}, {"role": "data_generation", "definition_id": "clinical_trial", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["or sterile water for 24 h. IMQ-treated mice were randomized to receive either 3-BrPA (100μL of 1 mg/mL), 1%"], "order_basis": "paper_text_order:3953", "id": "assay:6"}]}