Benzyl isothiocyanate provokes senolysis by targeting AKT in senescent IPF fibroblasts and reverses persistent pulmonary fibrosis in aged mice
IntroductionSenescent cells (SCs) accumulate with age and play a causative role in age-related diseases, such as idiopathic pulmonary fibrosis (IPF). Clearance of SCs attenuates lung fibrogenesis and favors fibrosis resolution, suggesting that targeting of SCs is recognized as a promising therapeuti...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1506518/full |
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| author | Rui Wang Fan Yang Ying Liu Meiting Peng Lu Yu Qinhui Hou Yuan Liu Zhenshun Cheng Zhenshun Cheng Zhenshun Cheng |
| author_facet | Rui Wang Fan Yang Ying Liu Meiting Peng Lu Yu Qinhui Hou Yuan Liu Zhenshun Cheng Zhenshun Cheng Zhenshun Cheng |
| author_sort | Rui Wang |
| collection | DOAJ |
| description | IntroductionSenescent cells (SCs) accumulate with age and play a causative role in age-related diseases, such as idiopathic pulmonary fibrosis (IPF). Clearance of SCs attenuates lung fibrogenesis and favors fibrosis resolution, suggesting that targeting of SCs is recognized as a promising therapeutic approach for IPF. Isothiocyanates (ITCs) are natural compounds with anticancer and anti-aging properties, but their role in IPF remains unclear. The aim of our study to investigate whether benzyl isothiocyanate (BITC), a type of ITCs, can act as a senolytic agent thereby attenuating pulmonary fibrosis in aged mice.MethodsPrimary lung fibroblasts from IPF patients and controls were cultured and treated with various ITCs to identify potential senolytic agents. Senescence-associated β-galactosidase staining, Cell viability assays, Annexin V/PI double staining, Caspase 3 activity assay, Western blot analysis, and qPCR were performed to evaluate senescence markers, cell viability, and apoptosis-related proteins after BITC treatment of senescent IPF lung fibroblasts in vitro. HE staining, Masson staining, Hydroxyproline assay, and Western blot analysis were used to assess the pathological progress, collagen content of lung tissues, and fibrotic gene expression changes after BITC treatment in C57BL/6 aged mice.ResultsUsing senescent IPF fibroblasts, we screened and identified BITC as a potent senolytic drug. We show that BITC selectively induces apoptosis in senescent IPF fibroblasts by targeting AKT signal pathway. Intraperitoneal administration of BITC to an age-related lung fibrosis mouse model effectively depleted senescent lung fibroblasts and reversed persistent pulmonary fibrosis.DiscussionOur study reveals that BITC may be a promising therapeutic option for IPF and other age-related disease that progress with the accumulation of senescent fibroblasts. |
| format | Article |
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| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-aef9dcc005b244c3b93e601ad17f138c2025-08-20T03:51:58ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15065181506518Benzyl isothiocyanate provokes senolysis by targeting AKT in senescent IPF fibroblasts and reverses persistent pulmonary fibrosis in aged miceRui Wang0Fan Yang1Ying Liu2Meiting Peng3Lu Yu4Qinhui Hou5Yuan Liu6Zhenshun Cheng7Zhenshun Cheng8Zhenshun Cheng9Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaWuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, ChinaHubei Engineering Center for Infectious Disease Prevention, Control and Treatment, Wuhan, ChinaIntroductionSenescent cells (SCs) accumulate with age and play a causative role in age-related diseases, such as idiopathic pulmonary fibrosis (IPF). Clearance of SCs attenuates lung fibrogenesis and favors fibrosis resolution, suggesting that targeting of SCs is recognized as a promising therapeutic approach for IPF. Isothiocyanates (ITCs) are natural compounds with anticancer and anti-aging properties, but their role in IPF remains unclear. The aim of our study to investigate whether benzyl isothiocyanate (BITC), a type of ITCs, can act as a senolytic agent thereby attenuating pulmonary fibrosis in aged mice.MethodsPrimary lung fibroblasts from IPF patients and controls were cultured and treated with various ITCs to identify potential senolytic agents. Senescence-associated β-galactosidase staining, Cell viability assays, Annexin V/PI double staining, Caspase 3 activity assay, Western blot analysis, and qPCR were performed to evaluate senescence markers, cell viability, and apoptosis-related proteins after BITC treatment of senescent IPF lung fibroblasts in vitro. HE staining, Masson staining, Hydroxyproline assay, and Western blot analysis were used to assess the pathological progress, collagen content of lung tissues, and fibrotic gene expression changes after BITC treatment in C57BL/6 aged mice.ResultsUsing senescent IPF fibroblasts, we screened and identified BITC as a potent senolytic drug. We show that BITC selectively induces apoptosis in senescent IPF fibroblasts by targeting AKT signal pathway. Intraperitoneal administration of BITC to an age-related lung fibrosis mouse model effectively depleted senescent lung fibroblasts and reversed persistent pulmonary fibrosis.DiscussionOur study reveals that BITC may be a promising therapeutic option for IPF and other age-related disease that progress with the accumulation of senescent fibroblasts.https://www.frontiersin.org/articles/10.3389/fphar.2025.1506518/fullidiopathic pulmonary fibrosiscellular senescencesenolysisbenzyl isothiocyanatefibroblasts |
| spellingShingle | Rui Wang Fan Yang Ying Liu Meiting Peng Lu Yu Qinhui Hou Yuan Liu Zhenshun Cheng Zhenshun Cheng Zhenshun Cheng Benzyl isothiocyanate provokes senolysis by targeting AKT in senescent IPF fibroblasts and reverses persistent pulmonary fibrosis in aged mice Frontiers in Pharmacology idiopathic pulmonary fibrosis cellular senescence senolysis benzyl isothiocyanate fibroblasts |
| title | Benzyl isothiocyanate provokes senolysis by targeting AKT in senescent IPF fibroblasts and reverses persistent pulmonary fibrosis in aged mice |
| title_full | Benzyl isothiocyanate provokes senolysis by targeting AKT in senescent IPF fibroblasts and reverses persistent pulmonary fibrosis in aged mice |
| title_fullStr | Benzyl isothiocyanate provokes senolysis by targeting AKT in senescent IPF fibroblasts and reverses persistent pulmonary fibrosis in aged mice |
| title_full_unstemmed | Benzyl isothiocyanate provokes senolysis by targeting AKT in senescent IPF fibroblasts and reverses persistent pulmonary fibrosis in aged mice |
| title_short | Benzyl isothiocyanate provokes senolysis by targeting AKT in senescent IPF fibroblasts and reverses persistent pulmonary fibrosis in aged mice |
| title_sort | benzyl isothiocyanate provokes senolysis by targeting akt in senescent ipf fibroblasts and reverses persistent pulmonary fibrosis in aged mice |
| topic | idiopathic pulmonary fibrosis cellular senescence senolysis benzyl isothiocyanate fibroblasts |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1506518/full |
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