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SNHG9, delivered by adipocyte-derived exosomes, alleviates inflammation and apoptosis of endothelial cells through suppressing TRADD expression.

Abstract：

:Exosomes are membrane-derived vesicles and play a critical role in cell signaling by transferring RNAs and proteins to target cells through fusion with the cell membrane. Long non-coding RNA-small nucleolar RNA host gene 9 (lncRNA-SNHG9) was proven to be an important element in lncRNA-mRNA interaction networks during adipocyte differentiation, suggesting its potential involvement in the development of obesity, an important risk factor of cardiovascular and cerebrovascular endothelial dysfunction. However, the role of lncRNA-SNHG9 within the exosome in endothelial dysfunction of obese patients is largely unknown. In this study, we proved that adipocytes-derived exosomal SNHG9 were downregulated in obese persons and further decreased in obese individuals with endothelial dysfunction. Functional experimentations demonstrated that adipocytes-derived exosomal SNHG9 alleviated inflammation and apoptosis in endothelial cells. Bioinformatic analysis revealed that there was a potential interaction between SNHG9 and the TNF receptor type 1-associated death domain protein (TRADD) mRNA. Then, RNA-binding protein immunoprecipitation assay based on Ago2 antibody and ribonuclease protection assay demonstrated that exosomal SNHG9 directly bound to a specific region in TRADD mRNA sequence and formed an RNA dimeric inducible silencing complex. Moreover, knockdown of TRADD markedly inhibited inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs), whereas overexpression of TRADD dramatically neutralized the protective effect of exosomal SNHG9 on epithelial dysfunction. Therefore, SNHG9 could prevent endothelial dysfunction in obese patients by suppressing inflammation and apoptosis, indicating that SNHG9 may be a potential therapeutic target for obese patients with endothelial dysfunction.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Song Y,Li H,Ren X,Li H,Feng C

doi

10.1016/j.ejphar.2020.172977

subject

Has Abstract

pub_date

2020-04-05 00:00:00

pages

172977

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(20)30069-8

journal_volume

872

pub_type

杂志文章

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SNHG9, delivered by adipocyte-derived exosomes, alleviates inflammation and apoptosis of endothelial cells through suppressing TRADD expression.