Biology direct · 2026
PDZK1 is downregulated in ovariectomized mice with angiotensin II-induced hypertension and interacts with β2-AR to regulate endothelial ERK1/2/c-Fos signaling.
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.
Zhang Haoran, Meng Yan, Zheng Wenjing, Bu Wenjie, Liu Wenxiu, Zhang Xiaohui, Shi Zhiyu, Liu Chunnan, Zhao Meng, Wang Huiying, Bai Yufeng, Zhao Dechao, Chi Jinyu
Аннотация
BACKGROUND: Estrogen deficiency is a major risk factor for postmenopausal hypertension. PDZK1, an estrogen-responsive scaffold protein, may interact with the β2-adrenergic receptor (β2-AR) to regulate vascular function, but this axis has not been characterized in the context of estrogen-deficient hypertension.
METHODS: We used ovariectomized and PDZK1 knockout mice infused with angiotensin II to model hypertension in vivo, and HUVECs for mechanistic studies in vitro. Techniques included hemodynamic measurements, histology, molecular interaction assay, chromatin immunoprecipitation, and functional cellular assays.
RESULTS: Ovariectomy exacerbated Ang II-induced hypertension and vascular remodeling, which correlated with reduced PDZK1 expression. PDZK1 KO mice showed enhanced hypertensive responses and impaired endothelium-dependent relaxation. Mechanistically, PDZK1 interacted with β2-AR via its PDZ1 and PDZ4 domains, stabilizing β2-AR and activating the downstream ERK1/2/c-Fos pathway to promote endothelial proliferation. PDZK1 knockdown or β2-AR inhibition attenuated this signaling and suppressed endothelial repair.
CONCLUSION: Our study identifies a novel PDZK1/β2-AR/ERK1/2/c-Fos axis that is essential for maintaining endothelial function under estrogen-sufficient conditions. Disruption of this pathway in the context of estrogen deficiency contributes to hypertension, highlighting PDZK1 as a potential therapeutic target for postmenopausal hypertension.
METHODS: We used ovariectomized and PDZK1 knockout mice infused with angiotensin II to model hypertension in vivo, and HUVECs for mechanistic studies in vitro. Techniques included hemodynamic measurements, histology, molecular interaction assay, chromatin immunoprecipitation, and functional cellular assays.
RESULTS: Ovariectomy exacerbated Ang II-induced hypertension and vascular remodeling, which correlated with reduced PDZK1 expression. PDZK1 KO mice showed enhanced hypertensive responses and impaired endothelium-dependent relaxation. Mechanistically, PDZK1 interacted with β2-AR via its PDZ1 and PDZ4 domains, stabilizing β2-AR and activating the downstream ERK1/2/c-Fos pathway to promote endothelial proliferation. PDZK1 knockdown or β2-AR inhibition attenuated this signaling and suppressed endothelial repair.
CONCLUSION: Our study identifies a novel PDZK1/β2-AR/ERK1/2/c-Fos axis that is essential for maintaining endothelial function under estrogen-sufficient conditions. Disruption of this pathway in the context of estrogen deficiency contributes to hypertension, highlighting PDZK1 as a potential therapeutic target for postmenopausal hypertension.