Ac‐SDKP modulates apoptosis via HSP27 and the FAS/FASL and mitochondrial axes
6 affiliations
- 1School of Basic Medical Sciences North China University of Science and Technology Tangshan China
- 2Hebei Key Laboratory for Chronic Diseases North China University of Science and Technology Tangshan China
- 3Department of Breast Surgery Tangshan Central Hospital Tangshan Hebei China
- 4Department of Clinical Laboratory The Third Central Hospital of Tianjin (Tianjin University Central Hospital) Tianjin China
- 5Department of Research Management Yutian County Hospital of Traditional Chinese Medicine Tangshan China
- 6Department of Clinical Microbiology Hospital of North China University of Science and Technology Tangshan China
Abstract
Background: Silicosis is a progressive, irreversible fibrotic lung disease caused by long‐term exposure to crystalline silica. Although the anti‐fibrotic tetrapeptide Ac‐SDKP has shown promise in reducing fibrosis, the specific molecular mechanisms through which it modulates apoptosis in silica‐induced lung injury remain unclear, particularly the role of heat shock protein 27 (HSP27).
Methods: Wistar rats were divided into groups including control, model (2‐week, 3‐week, and 4‐week), and Ac‐SDKP prevention/treatment groups. In vitro, MEF and A549 cells were treated with TGF‐β1 and Ac‐SDKP to observe the effects on apoptosis‐related proteins. Additionally, HSP27 interference vectors were constructed to study its role in regulating apoptosis via FAS/FASL and mitochondrial pathways in both in vivo and in vitro models.
Results: In vivo, Ac‐SDKP administration alleviated silica‐induced pulmonary fibrosis and reduced apoptosis in lung tissue. In contrast, in vitro, TGF‐β1 stimulation suppressed apoptosis in A549 and MEF cells, whereas Ac‐SDKP restored apoptotic activity by regulating the HSP27‐mediated FAS/FASL and mitochondrial pathways. Moreover, AAV9‐mediated knockdown of HSP27 in mice enhanced apoptosis and attenuated fibrosis, confirming the anti‐apoptotic role of HSP27 in silicosis.
Conclusion: These findings reveal that Ac‐SDKP exerts context‐dependent modulation of apoptosis through HSP27—protecting acutely injured alveolar epithelial cells in vivo while reinstating apoptotic signaling in EMT‐adapted A549 and MEF cells in vitro. Thus, targeting HSP27 may offer a promising therapeutic strategy to restore apoptotic–fibrotic equilibrium in silicosis and related pulmonary fibrotic disorders.
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BibTeX
@article{guo2026acsdkp,
title = {{Ac‐SDKP modulates apoptosis via HSP27 and the FAS/FASL and mitochondrial axes}},
author = {Wenxin Guo and Jinyin Yan and Wenli Li and Jin Wang and Lu Liu and Chengmei Zhang and Wei Cao and Shanshan Yao and Haibo Gong and Yi He and Zihan Zhou and Siyan Chen and Li Feng and Haijing Deng},
journal = {Animal Models and Experimental Medicine},
year = {2026},
month = aug,
doi = {10.1002/ame2.70272},
url = {https://doi.org/10.1002/ame2.70272},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Ac‐SDKP modulates apoptosis via HSP27 and the FAS/FASL and mitochondrial axes
AU - Wenxin Guo
AU - Jinyin Yan
AU - Wenli Li
AU - Jin Wang
AU - Lu Liu
AU - Chengmei Zhang
AU - Wei Cao
AU - Shanshan Yao
AU - Haibo Gong
AU - Yi He
AU - Zihan Zhou
AU - Siyan Chen
AU - Li Feng
AU - Haijing Deng
PY - 2026
DA - 2026/08/06
JO - Animal Models and Experimental Medicine
DO - 10.1002/ame2.70272
UR - https://doi.org/10.1002/ame2.70272
AB - Background: Silicosis is a progressive, irreversible fibrotic lung disease caused by long‐term exposure to crystalline silica. Although the anti‐fibrotic tetrapeptide Ac‐SDKP has shown promise in reducing fibrosis, the specific molecular mechanisms through which it modulates apoptosis in silica‐induced lung injury remain unclear, particularly the role of heat shock protein 27 (HSP27). Methods: Wistar rats were divided into groups including control, model (2‐week, 3‐week, and 4‐week), and Ac‐SDKP prevention/treatment groups. In vitro, MEF and A549 cells were treated with TGF‐β1 and Ac‐SDKP to observe the effects on apoptosis‐related proteins. Additionally, HSP27 interference vectors were constructed to study its role in regulating apoptosis via FAS/FASL and mitochondrial pathways in both in vivo and in vitro models. Results: In vivo, Ac‐SDKP administration alleviated silica‐induced pulmonary fibrosis and reduced apoptosis in lung tissue. In contrast, in vitro, TGF‐β1 stimulation suppressed apoptosis in A549 and MEF cells, whereas Ac‐SDKP restored apoptotic activity by regulating the HSP27‐mediated FAS/FASL and mitochondrial pathways. Moreover, AAV9‐mediated knockdown of HSP27 in mice enhanced apoptosis and attenuated fibrosis, confirming the anti‐apoptotic role of HSP27 in silicosis. Conclusion: These findings reveal that Ac‐SDKP exerts context‐dependent modulation of apoptosis through HSP27—protecting acutely injured alveolar epithelial cells in vivo while reinstating apoptotic signaling in EMT‐adapted A549 and MEF cells in vitro. Thus, targeting HSP27 may offer a promising therapeutic strategy to restore apoptotic–fibrotic equilibrium in silicosis and related pulmonary fibrotic disorders.
SN - 2096-5451
SN - 2576-2095
ER -