2. Academic Validation
  3. NLRP3 inflammasome-mediated Pyroptosis induce Notch signal activation in endometriosis angiogenesis

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

  • Mol Cell Endocrinol. 2023 May 31;111952. doi: 10.1016/j.mce.2023.111952.
Minyi Zhang 1,  Zhimian Shi 1,  Xianglan Peng 2,  Dongpeng Cai 1,  Rui Peng 2,  Yike Lin 1,  Linfeng Dai 1,  Jieyi Li 1,  Yulin Chen 1,  Jing Xiao 3,  Su Dong 4,  Wei Wang 5,  Yang Chen 6,  Hong He 7
Affiliations

Affiliations

  • 1 School of Pharmaceutical, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China.
  • 2 Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China.
  • 3 The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, Guangdong, China.
  • 4 Department of Pharmacy, People's Hospital of Dongxihu District, Wuhan, 430040, Hubei, China.
  • 5 School of Pharmaceutical, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China. Electronic address: [email protected].
  • 6 School of Pharmaceutical, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China. Electronic address: [email protected].
  • 7 Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China. Electronic address: [email protected].
PMID: 37268099 DOI: 10.1016/j.mce.2023.111952
Abstract

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 NICD 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.

Keywords

Angiogenesis; Endometriosis; NLRP3 inflammasome; Notch1 signal; Pyroptosis.

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