ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Respiratory Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1506518
This article is part of the Research TopicAcute and Chronic Lung Injury: Therapeutic Targets and DrugsView all 6 articles
Benzyl isothiocyanate provokes senolysis by targeting AKT in senescent IPF fibroblasts and reverses persistent pulmonary fibrosis in aged mice
Provisionally accepted
- Zhongnan Hospital, Wuhan University, Wuhan, China
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Senescent 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. Using senescent IPF fibroblasts, we screened and identified benzyl isothiocyanate (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. Our results demonstrate that BITC may be a promising therapeutic option for IPF and other age-related disease that progress with the accumulation of senescent fibroblasts.
Keywords: Idiopathic Pulmonary Fibrosis, cellular senescence, Senolysis, Benzyl isothiocyanate Abbreviations α-SMA, α-smooth muscle actin, Bax, BCL2-Associated X, Bcl2, B-cell lymphoma 2, BLM, bleomycin, BITC, benzyl isothiocyanate
Received: 05 Oct 2024; Accepted: 23 Apr 2025.
Copyright: © 2025 Wang, Yang, Liu, Peng, Yu, Hou, Liu and Cheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yuan Liu, Zhongnan Hospital, Wuhan University, Wuhan, China
Zhenshun Cheng, Zhongnan Hospital, Wuhan University, Wuhan, China
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