{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:08:33Z","timestamp":1785434913618,"version":"3.56.0"},"reference-count":66,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130054"],"award-info":[{"award-number":["82130054"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82130054"],"award-info":[{"award-number":["82130054"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is a fatal vascular disorder with poor prognosis. 6:2 chloro-polyfluorooctane ether sulfonate (F-53B), a persistent environmental contaminant detected in humans, is known to be vasculotoxic, yet its association with PAH remains unexplored. This study aims to elucidate the mechanisms linking F-53B exposure to PAH by integrating network toxicology, molecular docking and in vitro experiments. Potential F-53B targets were predicted using ChEMBL, PharmMapper, and TargetNet. PAH-related genes were compiled from GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and GSE254617. We identified 42 key targets of F-53B-related PAH. Functional enrichment revealed terms such as inflammatory response and extracellular matrix. Protein\u2013protein interaction (PPI) analysis identified five hub genes: CCL2, CXCL8, CCL5, CCR2, and CCL11. Molecular docking confirmed strong binding between F-53B and these core targets, with CCR2 showing the strongest affinity (\u221210 kcal\/mol). Molecular dynamics simulations further verified stable binding to CCR2. In vitro experiments demonstrated that F-53B activated the CCL2\/CCR2 axis and induced IL-1\u03b2, TNF-\u03b1, and IL-6 in HUVECs and RAW264.7 cells. This study reveals that F-53B is linked to PAH through dysregulation of chemokine signaling networks and induction of inflammatory cytokines. These findings suggest F-53B as a potential environmental risk factor for PAH and pinpoint potential targets for intervention.<\/jats:p>","DOI":"10.3390\/toxics14060477","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:25:31Z","timestamp":1780399531000},"page":"477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the Potential Effects of F-53B on Pulmonary Arterial Hypertension Through Network Toxicology, Molecular Docking, and In Vitro Validation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2580-9591","authenticated-orcid":false,"given":"Lingling","family":"Xu","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3954-1013","authenticated-orcid":false,"given":"Yujie","family":"Ma","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2296-7725","authenticated-orcid":false,"given":"Zhenming","family":"Zheng","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zou","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106099","DOI":"10.1016\/j.rmed.2020.106099","article-title":"Evaluation and management of pulmonary arterial hypertension","volume":"171","author":"Beshay","year":"2020","journal-title":"Respir. 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