{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:06:26Z","timestamp":1779455186666,"version":"3.53.1"},"reference-count":33,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Young Scientists Fund of the Natural Science Foundation of Xinjiang Uygur Autonomous Region","award":["2024D01C310"],"award-info":[{"award-number":["2024D01C310"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Liver diseases cause more than 2 million annual deaths globally, accounting for 4% of the total global mortality rate. Hepatic fibrosis (HF) acts as an indispensable pathological mediator in the progressive deterioration of chronic liver diseases. Thus, the identification of effective anti-fibrotic targets and rational development of corresponding therapeutic agents are expected to deliver profound clinical value for patients suffering from chronic liver disorders. Methods: An in vivo HF model was established to detect Kupffer cell (KC) polarization and periostin (POSTN) protein expression. In vitro, the CCK-8 (Cell Counting Kit-8) assay was applied to evaluate the regulatory effects of Postn-knockdown macrophages on LX-2 cell activity. Conditional knockout mice with Postn were constructed in vivo, and liver tissue samples were used for single-cell sequencing. Functional enrichment and cell differentiation prediction analyses were performed. CellChat was further utilized to characterize alterations in intercellular communication between Postn-deficient KCs and adjacent liver cells. Finally, POSTN-targeted inhibitors were screened and validated via virtual drug screening and experiments. Results: In the HF model, the M2 polarization of KCs\u00a0was associated with\u00a0the upregulated expression of POSTN. In contrast, in vitro Postn knockdown\u00a0correlated with\u00a0significantly suppressed LX-2 cell activation. Single-cell profiling\u00a0suggests that\u00a0Postn deficiency in Kupffer cells\u00a0is linked to\u00a0remodeling of the hepatic microenvironment. In drug repurposing, Rhodiosin exhibited binding affinity to POSTN and\u00a0was observed to\u00a0inhibit macrophage M2 polarization.\u00a0Conclusions:\u00a0POSTN\u00a0may contribute to\u00a0KC M2 polarization\u00a0and be associated with\u00a0remodeling of the intercellular interaction network among liver cells. Rhodiosin, as a POSTN-binding compound,\u00a0shows potential\u00a0for anti-hepatic fibrotic effects.<\/jats:p>","DOI":"10.3390\/ph19050752","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:14:52Z","timestamp":1779452092000},"page":"752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Mechanism of POSTN Mediating M2 Polarization of Kupffer Cells to Promote Hepatic Fibrosis"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0855-5638","authenticated-orcid":false,"given":"Meng-Dan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi 830091, China"},{"name":"Xinjiang Key Laboratory of Biopharmaceuticals and Medical Devices, Urumqi 830001, China"},{"name":"Engineering Research Center of Xinjiang and Central Asian Medicine Resources, Ministry of Education, Urumqi 830017, China"},{"name":"Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Urumqi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo-Ying","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi 830091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9651-1612","authenticated-orcid":false,"given":"Arzu","family":"Mijit","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi 830091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton, FL 33431, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6505-2643","authenticated-orcid":false,"given":"Yang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi 830091, China"},{"name":"School of Public Health, Xinjiang Medical University, Urumqi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Feng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi 830091, China"},{"name":"Xinjiang Key Laboratory of Biopharmaceuticals and Medical Devices, Urumqi 830001, China"},{"name":"Engineering Research Center of Xinjiang and Central Asian Medicine Resources, Ministry of Education, Urumqi 830017, China"},{"name":"Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Urumqi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J. 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