Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
SYVN1-provoked RASA1 ubiquitination promotes pulmonary inflammation in chronic obstructive pulmonary disease.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wu Ju-Hong, Ma Yi-Cheng, Wang Yu-Qi, Miao Hai-Long, Liu Meng-Xue, Hua Dong-Xu, Tang Min-Min, Sui Tian-Rui, Wu Zhi-Yong, Wang Yu, Yang Jin, Zhao Hui, Fei Jun, Zhao Xu-Dong, Zhang Fang, Fu Lin, Cao Wei
Аннотация
BACKGROUND AND OBJECTIVE: Ras p21 protein activator 1 (RASA1) is mainly located on cytoplasm and can regulate GTPase activity. The goal of this study was to analyze the association between pulmonary RASA1 expression and chronic obstructive pulmonary disease (COPD) and the potential mechanisms.
METHODS: COPD patients and age- and sex-matched control subjects were enrolled. In addition, cigarette smoke (CS) evoked-COPD model in mice and cigarette smoke extract (CSE)-exposed BEAS-2B cells were used.
RESULTS: Pulmonary RASA1 expression was reduced compared with control subjects and gradually decreased in parallel with the severity of COPD patients. Correlative analysis found pulmonary RASA1 was positively associated with pulmonary function parameters and inversely correlated with inflammatory cytokines among COPD patients. RASA1 protein expression was downregulated in lung tissues of CS-evoked COPD mice and CSE-exposed BEAS-2B cells. RAS/PI3K/Akt signaling was activated in lung tissues of COPD patients and mice, as well as BEAS-2B cells after CSE treatment. There was a negative correlation between SYVN1 and RASA1 in lung tissues of COPD patients. Mechanistically, CSE exposure enhanced RASA1 proteasome degradation through elevating E3 ubiquitin ligase SYVN1. CS exposure facilitated inflammatory cytokines production via activating RAS/PI3K/Akt signaling. Genetic deletion of SYVN1 alleviated CSE-provoked inflammatory response via inhibiting RAS/PI3K/Akt signaling in BEAS-2B cells.
CONCLUSION: These data revealed that E3 ubiquitin ligase SYVN1-provoked RASA1 proteasome degradation involves in inflammatory response through activating RAS/PI3K/Akt signaling in the process of COPD.
METHODS: COPD patients and age- and sex-matched control subjects were enrolled. In addition, cigarette smoke (CS) evoked-COPD model in mice and cigarette smoke extract (CSE)-exposed BEAS-2B cells were used.
RESULTS: Pulmonary RASA1 expression was reduced compared with control subjects and gradually decreased in parallel with the severity of COPD patients. Correlative analysis found pulmonary RASA1 was positively associated with pulmonary function parameters and inversely correlated with inflammatory cytokines among COPD patients. RASA1 protein expression was downregulated in lung tissues of CS-evoked COPD mice and CSE-exposed BEAS-2B cells. RAS/PI3K/Akt signaling was activated in lung tissues of COPD patients and mice, as well as BEAS-2B cells after CSE treatment. There was a negative correlation between SYVN1 and RASA1 in lung tissues of COPD patients. Mechanistically, CSE exposure enhanced RASA1 proteasome degradation through elevating E3 ubiquitin ligase SYVN1. CS exposure facilitated inflammatory cytokines production via activating RAS/PI3K/Akt signaling. Genetic deletion of SYVN1 alleviated CSE-provoked inflammatory response via inhibiting RAS/PI3K/Akt signaling in BEAS-2B cells.
CONCLUSION: These data revealed that E3 ubiquitin ligase SYVN1-provoked RASA1 proteasome degradation involves in inflammatory response through activating RAS/PI3K/Akt signaling in the process of COPD.