NLRP3 inflammasome-mediated Pyroptosis induce Notch signal activation in endometriosis angiogenesis

• Published in: Molecular and cellular endocrinology Vol. 574; p. 111952
• Main Authors: Zhang, Minyi, Shi, Zhimian, Peng, Xianglan, Cai, Dongpeng, Peng, Rui, Lin, Yike, Dai, Linfeng, Li, Jieyi, Chen, Yulin, Xiao, Jing, Dong, Su, Wang, Wei, Chen, Yang, He, Hong
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 20.08.2023
• Subjects: Angiogenesis; Animals; carcinogenesis; endocrinology; Endometriosis; endometrium; Endothelial Cells - metabolism; Female; Humans; inflammasomes; Inflammasomes - metabolism; Mice; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasome; Notch1 signal; pain; Pyroptosis; risk; Signal Transduction; Angiogenesis; Endometriosis; Notch1 signal; Pyroptosis; NLRP3 inflammasome
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/j.mce.2023.111952

Endometriosis is characterized by the presence of endometrial tissue outside the uterus that not only causes severe pelvic pain and infertility but also increased risk for ovarian carcinogenesis in women of reproductive age. Here, we found that angiogenesis was increased and accompanied with up-regulation of Notch1 in human endometriotic tissue sample, which is associated with pyroptosis induced by activation of endothelial NLRP3 inflammasome. Further, in endometriosis model induced in wild type and NLRP3-deficient (NLRP3-KO) mice, we found that deficiency of NLRP3 suppressing the development of endometriosis. In vitro, inhibiting the activation of NLRP3 inflammasome prevents LPS/ATP-induced tube formation in endothelial cells. Meanwhile, knockdown NLRP3 expression by gRNA disrupt the interaction between Notch1 and HIF-1α under the inflammatory microenvironment. This study demonstrates that activation of NLRP3 inflammasome-mediated pyroptosis affects angiogenesis in endometriosis via Notch1-dependent manner. •Activation of NLRP3 inflammasome played a central role in the development of endometriosis angiogenesis.•NLRP3 inflammasome induced angiogenesis through Notch1 signaling.•NLRP3 inflammasome regulated the interaction between Notch1 and HIF-1α.