Open AccessIgE Aggravates the Senescence of Smooth Muscle Cells in Abdominal Aortic Aneurysm by Upregulating LincRNA-p21
Author(s) -
Wenjun Guo,
Ran Gao,
Wei Zhang,
Weipeng Ge,
Meng Ren,
Bolun Li,
Hongmei Zhao,
Jing Wang
Publication year - 2019
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2018.1128
Subject(s) - immunoglobulin e , medicine , senescence , immunology , pathogenesis , gene knockdown , inflammation , in vivo , in vitro , mast cell , receptor , aortic aneurysm , antibody , biology , aneurysm , cell culture , biochemistry , microbiology and biotechnology , surgery , genetics
Immunoglobulin E (lgE) activates immunity by binding to mast cells and basophils. It is well-known that IgE and its receptor, FcɛR1, play a key role in the development of airway inflammation and remodeling in allergic asthma. Recent studies show that IgE also plays an important role in abdominal aortic aneurysm (AAA) pathogenesis. However, the mechanism by which IgE promotes AAA remains unclear. Here we report that in our mouse model, asthma-induced high level of IgE aggravated AAA, but IgE lost this effect on AAA in FcɛR1 -/- mice. Our in vitro study revealed that IgE induced smooth muscle cell senescence via upregulating lincRNA-p21 against p21 without altering expression of p53. By this mechanism, IgE accelerated AAA in ApoE -/- mice, which was blocked by knockdown of lincRNA-p21 in both vitro and vivo. This study suggests that IgE actives the lincRNAp21-p21 pathway to induce SMC senescence, which contributes to the formation of AAA, and lincRNA-p21 is a potential therapeutic target for AAA aggravated by asthma.