The Gut Microbiota Dysbiosis in Preeclampsia Contributed to Trophoblast Cell Proliferation, Invasion, and Migration via lncRNA BC030099/NF- κ B Pathway

Mediators Inflamm. 2022 Jun 24:2022:6367264. doi: 10.1155/2022/6367264. eCollection 2022.

Abstract

Background: Preeclampsia (PE) is the main reason of maternal and perinatal morbidity and mortality. Gut microbiota imbalance in PE patients is accompanied by elevated serum lipopolysaccharide (LPS) levels, but whether it affects the occurrence and development of PE, the underlying mechanism is not clear. This paper intends to investigate the relationship between lncRNA BC030099, inflammation, and gut microbiota in PE.

Methods: The feces of the patients were collected, and gut microbiota changes were assessed by 16S rRNA sequencing and pathway analysis by PICRUSt. Next, we examined LPS and lncRNA BC030099 levels in feces or placenta of PE patients. Then, we knocked down lncRNA BC030099 in HTR-8/SVneo cells and added the NF-κB pathway inhibitor JSH-23. CCK-8 and Transwell assays were performed to determine cell proliferation, migration, and invasion. Western blot was utilized to evaluate MMP2, MMP9, snail, and E-cadherin, p-IκBα, IκBα, and nuclear NF-κB p65 levels. IL-6, IL-1β, and TNF-α levels were examined by ELISA.

Results: Gut microbiota was altered in PE patients, and microbial genes associated with LPS biosynthesis were significantly elevated in gut microbiota in the PE group. LPS level in feces and placenta of PE group was significantly elevated. lncRNA BC030099 level in placenta of PE group was also notably promoted. Knockdown of lncRNA BC030099 promoted HTR-8/SVneo cell proliferation, migration, and invasion. Knockdown of lncRNA BC030099 also elevated MMP2, MMP9, and snail levels and repressed E-cadherin level. In addition, lncRNA BC030099 affected NF-κB pathway. Furthermore, NF-κB inhibitor reversed HTR-8/SVneo cell proliferation, invasion, and migration induced by LPS.

Conclusions: The gut microbiota dysbiosis in PE contributed to HTR-8/SVneo cell proliferation, invasion, and migration via lncRNA BC030099/NF-κB pathway.

MeSH terms

  • Cadherins / metabolism
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Dysbiosis / metabolism
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Lipopolysaccharides / metabolism
  • Lipopolysaccharides / pharmacology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B / metabolism
  • Pre-Eclampsia* / genetics
  • Pre-Eclampsia* / metabolism
  • Pregnancy
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Ribosomal, 16S / metabolism
  • Trophoblasts / metabolism

Substances

  • Cadherins
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Long Noncoding
  • RNA, Ribosomal, 16S
  • NF-KappaB Inhibitor alpha
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9