Reproductive biomedicine online · 2026
Pyruvate carboxylase promotes progression of endometriosis by activating the AKT pathway.
СтатьяНазвание и аннотация: Перевод в очереди
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 Yongfeng, Ye Xiaoye, Jin Ou, Liu Beibei, Yu Shuchen, Zheng Aolin, Lv Fei, Zheng Yingling, Liu Fengjuan, Xu Song, Zhang Ke, Jin Chunyu, Tong Jinyi
Аннотация
RESEARCH QUESTION: Does pyruvate carboxylase drive the progression of endometriosis, and, if so, what is the underlying mechanism?
DESIGN: The expression of pyruvate carboxylase in clinical endometrial specimens was examined via immunohistochemistry. After knockdown or overexpression of pyruvate carboxylase in immortalized human endometriotic stromal cells (ihESC), cell proliferation and migration were assessed using 5-ethynyl-2'-deoxyuridine (EdU), colony formation and Transwell assays. Quasi-targeted metabolomics, RNA sequencing and western blotting were adopted to explore downstream molecular changes, and an allogeneic mouse endometriotic model was applied for in-vivo functional verification.
RESULTS: Expression of pyruvate carboxylase was up-regulated significantly in eutopic and ectopic endometrial tissues of patients with endometriosis compared with controls (P = 0.022 and P < 0.001, respectively). In-vitro and in-vivo experiments showed that pyruvate carboxylase promoted the progression of endometriosis. In addition, quasi-targeted metabolomics showed that knockdown of pyruvate carboxylase decreased the abundance of glycolytic metabolites in ihESC. Furthermore, RNA sequencing and western blotting identified that pyruvate carboxylase enhanced activity of the phosphoinositide-3-kinase-AKT pathway. Using AKT agonist (SC79) and inhibitor (AZD5363), pyruvate carboxylase was shown to modulate the expression of glycolytic enzymes and the progression of endometriosis through the AKT pathway. Finally, pyruvate carboxylase inhibitors ZY-444 and octyl gallate attenuated the progression of endometriosis.
CONCLUSIONS: Pyruvate carboxylase is up-regulated significantly in eutopic and ectopic endometrial tissues from patients with endometriosis, and modulates the expression of glycolytic enzymes as well as the progression of endometriosis via activation of the AKT pathway. These findings provide mechanistic insight into the metabolic reprogramming underlying the pathogenesis of endometriosis.
DESIGN: The expression of pyruvate carboxylase in clinical endometrial specimens was examined via immunohistochemistry. After knockdown or overexpression of pyruvate carboxylase in immortalized human endometriotic stromal cells (ihESC), cell proliferation and migration were assessed using 5-ethynyl-2'-deoxyuridine (EdU), colony formation and Transwell assays. Quasi-targeted metabolomics, RNA sequencing and western blotting were adopted to explore downstream molecular changes, and an allogeneic mouse endometriotic model was applied for in-vivo functional verification.
RESULTS: Expression of pyruvate carboxylase was up-regulated significantly in eutopic and ectopic endometrial tissues of patients with endometriosis compared with controls (P = 0.022 and P < 0.001, respectively). In-vitro and in-vivo experiments showed that pyruvate carboxylase promoted the progression of endometriosis. In addition, quasi-targeted metabolomics showed that knockdown of pyruvate carboxylase decreased the abundance of glycolytic metabolites in ihESC. Furthermore, RNA sequencing and western blotting identified that pyruvate carboxylase enhanced activity of the phosphoinositide-3-kinase-AKT pathway. Using AKT agonist (SC79) and inhibitor (AZD5363), pyruvate carboxylase was shown to modulate the expression of glycolytic enzymes and the progression of endometriosis through the AKT pathway. Finally, pyruvate carboxylase inhibitors ZY-444 and octyl gallate attenuated the progression of endometriosis.
CONCLUSIONS: Pyruvate carboxylase is up-regulated significantly in eutopic and ectopic endometrial tissues from patients with endometriosis, and modulates the expression of glycolytic enzymes as well as the progression of endometriosis via activation of the AKT pathway. These findings provide mechanistic insight into the metabolic reprogramming underlying the pathogenesis of endometriosis.