LPS-induced downregulation of microRNA-204/211 upregulates and stabilizes Angiopoietin-1 mRNA in EA.hy926 endothelial cells

Abstract

Angiopoietin-1 (ANG-1), a ligand of the endothelial cell-specific TIE2 surface receptor, acts in a complementary and coordinated manner with vascular endothelial growth factor during the process of angiogenesis. ANG-1 can be used as a clinically informative biomarker of disease severity and outcome in severe sepsis. The epithelium-specific Ets transcription factor 1 can activate ANG-1 transcription in the setting of inflammation; however, relatively little is known about the regulation of ANG-1 by microRNAs (miRs). It was observed that lipopolysaccharide (LPS) significantly increased ANG-1 mRNA and protein expression in EA.hy926 cells. ANG-1 was identified as a potential target gene of miR-204 and miR-211. Overexpression of miR-204/211 partially reversed the LPS-induced ANG-1 expression in EA.hy926 cells. Furthermore, overexpression of miR-204/211 significantly reduced the activity of a luciferase reporter gene containing the wild-type ANG-1 3′-untranslated region (UTR), but did not influence the activity of a luciferase reporter gene containing the ANG-1 3′-UTR with a mutated miR-204/211 binding site, confirming that miR-204/211 can bind to the ANG-1 3′-UTR and post-transcriptionally regulate ANG-1. Additionally, LPS enhanced the stability of ANG-1 mRNA by reducing the abundance of miR-204/211. Overexpression of miR-204/211 reduced the migration of EA.hy926 cells in vitro. The present study demonstrated that ANG-1 is a novel direct target gene of miR-204 and miR-211; in addition, LPS was able to inhibit this effect by reducing the expression of miR-204 and miR-211.

miR-204-5p and miR-211 Synergistically Downregulate the αS1-Casein Content and Contribute to the Lower Allergy of Goat Milk

“…Many studies have shown that miR-204-5p and miR-211 play similar roles in multiple biological processes. Melatonin or high phosphorus-induced miR-204/-211 attenuate vascular calcification and ageing in vascular smooth muscle cells. , miR-204/-211 are also involved in the process of human periodontal ligament stem cell chondrogenesis and umbilical vein endothelial cells angiogenesis . miR-204/-211 increase cellular growth and proliferation in breast cancer and melanoma by downregulating tumor suppressor genes.…”

Umbilical cord miRNAs to predict neonatal early onset sepsis

“…The role of miR-211-5p has not been well-studied in sepsis, but it has been implicated as a regulator of a variety of cellular processing including angiogenesis [ 18 ], maintenance of joint homeostasis [ 19 ], and autophagy-dependent apoptosis [ 20 ]. miR-211 has recently been proposed to play a role in sepsis modulation [ 21 ] as there is some evidence that miR-211 levels drop after exposure to LPS in cell culture [ 22 ] and that miR-211 could protect against inflammation in osteoarthritis [ 23 ]. In our study, miR-211 was upregulated in umbilical cord blood plasma, but not in the umbilical cord tissue.…”

LPS promotes the progression of sepsis by activation of lncRNA HULC/miR-204-5p/TRPM7 network in HUVECs

“…HULC plays an oncogene role in a variety of cancers [25,26], and a recent report revealed that increased HULC expression was related to LPS-induced inflammatory response and sepsis in endothelial cells [27]. Recently, the role of miR-204-5p in sepsis has been gradually explored, and it could target ANG-1 and be targeted by lncRNA NEAT1 to inhibit the damage of LPS on cells [28,29]. LncRNA generally functions as ceRNA of miRNA to regulate mRNA expression [30].…”