Heat shock protein 60 stimulates the migration of vascular smooth muscle cells via Toll-like receptor 4 and ERK MAPK activation

Zhao, Ying; Zhang, Chenxu; Wei, Xuge; Li, Pei; Cui, Ying; Qin, Yuanhua; Xin, Wei; Jin, Minli; Kohama, Kazuhiro; Gao, Ying

doi:10.1038/srep15352

Cited by 40 publications

(28 citation statements)

References 28 publications

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“…Additionally, HSP60, a cell-stress marker, has been proposed to trigger TLR4-mediated signalling in a vascular smooth muscle cell line, with implications in atherosclerosis. However, the effects of this protein have not been tested on platelets despite an increased expression of HSP60 on endothelial cells in sheer stress environments [ 94 , 95 ]. Serum amyloid A (SAA) is a potential ligand for TLR4 that is released, primarily from the liver, during an inflammatory response [ 96 , 97 ].…”

Section: Tlr4 Signalling In Plateletsmentioning

confidence: 99%

Toll-Like Receptor 4 Signalling and Its Impact on Platelet Function, Thrombosis, and Haemostasis

Vallance

Zeuner

Williams

et al. 2017

Mediators of Inflammation

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Platelets are anucleated blood cells that participate in a wide range of physiological and pathological functions. Their major role is mediating haemostasis and thrombosis. In addition to these classic functions, platelets have emerged as important players in the innate immune system. In particular, they interact with leukocytes, secrete pro- and anti-inflammatory factors, and express a wide range of inflammatory receptors including Toll-like receptors (TLRs), for example, Toll-like receptor 4 (TLR4). TLR4, which is the most extensively studied TLR in nucleated cells, recognises lipopolysaccharides (LPS) that are compounds of the outer surface of Gram-negative bacteria. Unlike other TLRs, TLR4 is able to signal through both the MyD88-dependent and MyD88-independent signalling pathways. Notably, despite both pathways culminating in the activation of transcription factors, TLR4 has a prominent functional impact on platelet activity, haemostasis, and thrombosis. In this review, we summarise the current knowledge on TLR4 signalling in platelets, critically discuss its impact on platelet function, and highlight the open questions in this area.

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Section: Tlr4 Signalling In Plateletsmentioning

confidence: 99%

Toll-Like Receptor 4 Signalling and Its Impact on Platelet Function, Thrombosis, and Haemostasis

Vallance

Zeuner

Williams

et al. 2017

Mediators of Inflammation

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“…We also examined the effects of siRNA-TMEM98 on the activity of ERK and expression of Cyclin D1. Activation of ERK signaling pathway was reported to mediate a range of cell fate decision, including cell proliferation, migration and transformation in VSMCs [ 22 – 25 ]. However, siRNA-TMEM98 did not markedly influence the activity of ERK1/2 in IL-8-treated AoSMC and A7r5 (Figure 5B-5F ).…”

Section: Resultsmentioning

confidence: 99%

“…Given that some key signaling pathways, such as PI3K/AKT, MAPK/ERK1/2 and CyclinD1 pathways indispensable for cell survival, cell cycle transition, migration and metabolism [ 22 – 25 , 34 – 36 ], we suspected whether there could be any degree of correlation occurring between TMEM98 functions and those above pathways. Our data showed that down-regulation of TMEM98 in VSMCs induced by IL-8 inhibited the expression of p-AKT, p-GSK-3β and Cyclin D1 respectively.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis

Zhu

Cai

et al. 2017

Oncotarget

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Transmembrane protein 98 (TMEM98), known as a novel gene related to lung cancer, hepatocellular carcinoma, differentiation of T helper 1 cells and normal eye development, has no defined role reported in terms of atherosclerosis (AS). To investigate the potential involvement of TMEM98 during AS processes, its obvious secretion and expression has been initially characterized in hyperlipidemia patients’ serum and AS mice's serum respectively. We then explored the possible role of TMEM98 in the pathogenesis of AS in vitro. IL-8, a pro-atherogenesis cytokine, was used to induce the expression of TMEM98 in both endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Collectively, TMEM98 expression significantly increased in ECs and VSMCs, both induced by IL-8. Additionally, the adhesion ability of monocytes to ECs as well as the proliferation and migration of VSMCs were all decreased after siRNA-TMEM98 treatment. Furthermore, siRNA-TMEM98 dramatically inhibited the expression of ICAM-1 in ECs and the expression of p-AKT, p-GSK3β and Cyclin D1 from VSMCs, and AKT agonist partially restored the proliferation and migration of VSMC after siRNA-TMEM98 treatment. Taken together, siRNA-TMEM98 inhibits IL-8 mediated EC adhesion by down-regulating the expression of ICAM-1. Additionally, it also hinders the proliferation and migration of VSMCs through suppressing the AKT/GSK3β/Cyclin D1 signaling pathway. Our study provides sufficient evidence to support that TMEM98 could be a novel gene associated with AS for the first time.

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“…In human epithelial cells, the exposure to PM2.5 from indoor dust activated autophagy through activating TLR4 and Nuclear Factor kappa-B (NFκB) [101]. Interestingly, TLR4 was assumed to mediate the inflammatory and remodeling stimulating effect of HSP60 in vascular smooth muscle cells [102]. The latter has been released by epithelial cells of asthma patients and triggered fibroblast remodeling and inflammation through increasing mitochondria number and activity [79].…”

Section: Mechanisms To Explain How Air Pollution Triggers Remodeling mentioning

confidence: 99%

Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma

Fang

Sun

Roth

2020

IJMS

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Asthma increases worldwide without any definite reason and patient numbers double every 10 years. Drugs used for asthma therapy relax the muscles and reduce inflammation, but none of them inhibited airway wall remodeling in clinical studies. Airway wall remodeling can either be induced through pro-inflammatory cytokines released by immune cells, or direct binding of IgE to smooth muscle cells, or non-immunological stimuli. Increasing evidence suggests that airway wall remodeling is initiated early in life by epigenetic events that lead to cell type specific pathologies, and modulate the interaction between epithelial and sub-epithelial cells. Animal models are only available for remodeling in allergic asthma, but none for non-allergic asthma. In human asthma, the mechanisms leading to airway wall remodeling are not well understood. In order to improve the understanding of this asthma pathology, the definition of “remodeling” needs to be better specified as it summarizes a wide range of tissue structural changes. Second, it needs to be assessed if specific remodeling patterns occur in specific asthma pheno- or endo-types. Third, the interaction of the immune cells with tissue forming cells needs to be assessed in both directions; e.g., do immune cells always stimulate tissue cells or are inflamed tissue cells calling immune cells to the rescue? This review aims to provide an overview on immunologic and non-immunologic mechanisms controlling airway wall remodeling in asthma.

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Heat shock protein 60 stimulates the migration of vascular smooth muscle cells via Toll-like receptor 4 and ERK MAPK activation

Cited by 40 publications

References 28 publications

Toll-Like Receptor 4 Signalling and Its Impact on Platelet Function, Thrombosis, and Haemostasis

Toll-Like Receptor 4 Signalling and Its Impact on Platelet Function, Thrombosis, and Haemostasis

Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis

Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma

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