Lipopolysaccharide acting via toll-like receptor 4 transactivates the TGF-β receptor in vascular smooth muscle cells

Rizwana Afroz; Hirushi Kumarapperuma; Quang V N Nguyen; Raafat Mohamed; Peter J Little; Danielle Kamato

doi:10.1007/s00018-022-04159-8

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Lipopolysaccharide acting via toll-like receptor 4 transactivates the TGF-β receptor in vascular smooth muscle cells

Journal article

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Lipopolysaccharide acting via toll-like receptor 4 transactivates the TGF-β receptor in vascular smooth muscle cells

Rizwana Afroz, Hirushi Kumarapperuma, Quang V N Nguyen, Raafat Mohamed, Peter J Little and Danielle Kamato

Cellular and Molecular Life Sciences, Vol.79(2), 121

2022

DOI: https://doi.org/10.1007/s00018-022-04159-8

PMID: 35122536

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Abstract

Transforming growth factor beta

Smad

Transactivation dependent

Toll-like receptors (TLRs) recognise pathogen‑associated molecular patterns, which allow the detection of microbial infection by host cells. Bacterial-derived toxin lipopolysaccharide activates TLR4 and leads to the activation of the Smad2 transcription factor. The phosphorylation of the Smad2 transcription factor is the result of the activation of the transforming growth factor-β receptor 1 (TGFBR1). Therefore, we sought to investigate LPS via TLR4-mediated Smad2 carboxy terminal phosphorylation dependent on the transactivation of the TGFBR1. The in vitro model used human aortic vascular smooth muscle cells to assess the implications of TLR4 transactivation of the TGFBR1 in vascular pathophysiology. We show that LPS-mediated Smad2 carboxy terminal phosphorylation is inhibited in the presence of TGFBR1 inhibitor, SB431542. Treatment with MyD88 and TRIF pathway antagonists does not affect LPS-mediated phosphorylation of Smad2 carboxy terminal; however, LPS-mediated Smad2 phosphorylation was inhibited in the presence of MMP inhibitor, GM6001, and unaffected in the presence of ROCK inhibitor Y27632 or ROS/NOX inhibitor DPI. LPS via transactivation of the TGFBR1 stimulates PAI-1 mRNA expression. TLRs are first in line to respond to exogenous invading substances and endogenous molecules; our findings characterise a novel signalling pathway in the context of cell biology. Identifying TLR transactivation of the TGFBR1 may provide future insight into the detrimental implications of pathogens in pathophysiology.

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Title: Lipopolysaccharide acting via toll-like receptor 4 transactivates the TGF-β receptor in vascular smooth muscle cells
Authors: Rizwana Afroz (Author) - Griffith University
Hirushi Kumarapperuma (Author) - The University of Queensland
Quang V N Nguyen (Author) - The University of Queensland
Raafat Mohamed (Author) - The University of Queensland
Peter J Little (Author) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - Legacy
Danielle Kamato (Corresponding Author) - The University of Queensland
Publication details: Cellular and Molecular Life Sciences, Vol.79(2), 121
Publisher: Birkhaeuser Science
Date published: 2022
DOI: 10.1007/s00018-022-04159-8
ISSN: 1420-9071; 1420-682X
PMID: 35122536
Copyright note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99610008602621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology

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