TNKS1BP1 mediates AECII senescence and radiation induced lung injury through suppressing EEF2 degradation.

Autor: Zhu J; Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Ao X; Hengyang Medical College, University of South China, Hengyang, 421001, China., Liu Y; Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Zhou S; Hengyang Medical College, University of South China, Hengyang, 421001, China., Hou Y; College of Life Sciences, Hebei University, Baoding, 071001, China., Yan Z; Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Zhou L; Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Chen H; Hengyang Medical College, University of South China, Hengyang, 421001, China., Wang P; Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Liang X; Hengyang Medical College, University of South China, Hengyang, 421001, China., Xie D; Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Gao S; Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Zhou PK; Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China. zhoupk@nic.bmi.ac.cn., Gu Y; Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China. yqgu96@163.com.; Hengyang Medical College, University of South China, Hengyang, 421001, China. yqgu96@163.com.; College of Life Sciences, Hebei University, Baoding, 071001, China. yqgu96@163.com.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2024 Aug 07; Vol. 25 (1), pp. 299. Date of Electronic Publication: 2024 Aug 07.
DOI: 10.1186/s12931-024-02914-y
Abstrakt: Background: Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI.
Results: Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI.
Conclusions: Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje