Academic Journal
Semaglutide exerts anti-pulmonary fibrosis effects by inhibiting cellular senescence through activation of the Sirt1/HSF1/HSPs pathway.
| Τίτλος: | Semaglutide exerts anti-pulmonary fibrosis effects by inhibiting cellular senescence through activation of the Sirt1/HSF1/HSPs pathway. |
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| Συγγραφείς: | Qian Z; Xiangya Nursing School, Central South University, 172 Tongzipo Road, Changsha 410013, Hunan, China., Shuang L; Xiangya Nursing School, Central South University, 172 Tongzipo Road, Changsha 410013, Hunan, China., Yu-Yang L; Xiangya Nursing School, Central South University, 172 Tongzipo Road, Changsha 410013, Hunan, China., Min-Lin L; Xiangya Nursing School, Central South University, 172 Tongzipo Road, Changsha 410013, Hunan, China., Chong-Mei H; School of Nursing, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750003, Ningxia, China., Min-Hui L; School of Nursing, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750003, Ningxia, China., Wei L; Xiangya Nursing School, Central South University, 172 Tongzipo Road, Changsha 410013, Hunan, China. Electronic address: liuw079@csu.edu.cn., Si-Yuan T; School of Nursing, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750003, Ningxia, China. Electronic address: sytang263@csu.edu.cn. |
| Πηγή: | Biochemical pharmacology [Biochem Pharmacol] 2026 Sep; Vol. 251 (Pt 2), pp. 118172. Date of Electronic Publication: 2026 Jun 18. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Elsevier Science Original Publication: Oxford, New York [etc.] Paragamon Press. |
| Ιατρικοί όροι (MeSH): | Cellular Senescence*/drug effects , Cellular Senescence*/physiology , Sirtuin 1*/metabolism , Heat Shock Transcription Factors*/metabolism , Heat Shock Transcription Factors*/genetics , Glucagon-Like Peptides*/pharmacology , Glucagon-Like Peptides*/therapeutic use , Pulmonary Fibrosis*/metabolism , Pulmonary Fibrosis*/drug therapy , Pulmonary Fibrosis*/chemically induced , Heat-Shock Proteins*/metabolism, Signal Transduction/drug effects ; Signal Transduction/physiology ; Animals ; Semaglutide ; Mice ; Male ; Mice, Inbred C57BL |
| Περίληψη: | Idiopathic pulmonary fibrosis is an interstitial lung disease of unknown etiology with no effective treatment. Semaglutide is a glucagon-like peptide-1 receptor agonist that has been widely used in the treatment of diabetes and obesity. This study investigated the therapeutic effects of semaglutide on pulmonary fibrosis and its molecular mechanisms. An in vivo mouse lung fibrosis model was established using bleomycin and treated with semaglutide, and the key targets of semaglutide were explored using heat shock factor 1 (HSF1) shRNA or Sirt1 inhibitor. In vitro, a mouse lung epithelial cell senescence model was established using hydrogen peroxide and treated with semaglutide. Key targets of semaglutide anti-senescence were screened by transcriptomics and the screened HSF1 genes were silenced using siRNA. Semaglutide-regulated HSPs were screened by transcriptomics and PCR arrays and co-immunoprecipitation experiments were conducted to explore key factors in semaglutide promoting increased expression of heat shock proteins (HSPs). We found that semaglutide significantly improved pulmonary fibrosis, oxidative stress and cellular senescence in vivo and inhibited hydrogen peroxide-induced cellular senescence in vitro. Moreover, the above effects were inhibited by silencing HSF1 or Sirt1 inhibition. In addition, semaglutide promoted HSF1 protein deacetylation by Sirt1, leading to the increased expression of HSPs downstream of HSF1. In conclusion, semaglutide inhibited cellular senescence and exerted anti-pulmonary fibrosis effects through the Sirt1 protein-mediated deacetylation of HSF1, which enhances HSF1 binding to the HSP gene promoters and increased the expression of various HSPs. (Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Cellular senescence; Pulmonary fibrosis; Semaglutide; Sirt1/HSF1/HSPs pathway |
| Substance Nomenclature: | 53AXN4NNHX (Semaglutide) EC 3.5.1.- (Sirtuin 1) 0 (Heat Shock Transcription Factors) EC 3.5.1.- (Sirt1 protein, mouse) 0 (Hsf1 protein, mouse) 62340-29-8 (Glucagon-Like Peptides) 0 (Heat-Shock Proteins) |
| Entry Date(s): | Date Created: 20260618 Date Completed: 20260722 Latest Revision: 20260722 |
| Update Code: | 20260723 |
| DOI: | 10.1016/j.bcp.2026.118172 |
| PMID: | 42315078 |
| Βάση Δεδομένων: | MEDLINE |
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