Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-020-74944-7
Title: Interleukin-11 is important for vascular smooth muscle phenotypic switching and aortic inflammation, fibrosis and remodeling in mouse models
Authors: Lim, W.-W.
Corden, B. 
Ng, B. 
Vanezis, K.
D’Agostino, G.
Widjaja, A.A. 
Song, W.-H.
Xie, C.
Su, L.
Kwek, X.-Y.
Tee, N.G.Z.
Dong, J. 
Ko, N.S.J.
Wang, M. 
Pua, C.J.
Jamal, M.H.
Soh, B.
Viswanathan, S. 
Schafer, S. 
Cook, S.A. 
Issue Date: 2020
Publisher: Nature Research
Citation: Lim, W.-W., Corden, B., Ng, B., Vanezis, K., D’Agostino, G., Widjaja, A.A., Song, W.-H., Xie, C., Su, L., Kwek, X.-Y., Tee, N.G.Z., Dong, J., Ko, N.S.J., Wang, M., Pua, C.J., Jamal, M.H., Soh, B., Viswanathan, S., Schafer, S., Cook, S.A. (2020). Interleukin-11 is important for vascular smooth muscle phenotypic switching and aortic inflammation, fibrosis and remodeling in mouse models. Scientific Reports 10 (1) : 17853. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-020-74944-7
Rights: Attribution 4.0 International
Abstract: Transforming growth factor beta-1 (TGFβ1) is a major driver of vascular smooth muscle cell (VSMC) phenotypic switching, an important pathobiology in arterial disease.We performed RNA-sequencing of TGFβ1-stimulated human aortic or arterial VSMCs which revealed large and consistent upregulation of Interleukin 11 (IL11). IL11 has an unknown function in VSMCs, which highly express the IL11 receptor alpha, suggestive of an autocrine loop. In vitro, IL11 activated ERK signaling, but inhibited STAT3 activity, and caused VSMC phenotypic switching to a similar extent as TGFβ1 or angiotensin II (ANGII) stimulation. Genetic or therapeutic inhibition of IL11 signaling reduced TGFβ1- or ANGII-induced VSMC phenotypic switching, placing IL11 activity downstream of these factors. Aortas of mice with Myh11-driven IL11 expression were remodeled and had reduced contractile but increased matrix and inflammatory genes expression. In two models of arterial pressure loading, IL11 was upregulated in the aorta and neutralizing IL11 antibodies reduced remodeling along with matrix and pro-inflammatory gene expression. These data show that IL11 plays an important role in VSMC phenotype switching, vascular inflammation and aortic pathobiology. © 2020, The Author(s).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/198997
ISSN: 2045-2322
DOI: 10.1038/s41598-020-74944-7
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1038_s41598_020_74944_7.pdf14.01 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

13
checked on Jun 25, 2022

WEB OF SCIENCETM
Citations

6
checked on Sep 23, 2021

Page view(s)

74
checked on Jun 23, 2022

Download(s)

1
checked on Jun 23, 2022

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons