Tryptase Promotes the Profibrotic Phenotype Transfer of Atrial Fibroblasts by PAR2 and PPARγ Pathway

Tan, H.S.; Chen, Zhisong; Chen, Fei; Yao, Yian; Liu, Yan; Xu, Wenjun; Liu, Xuebo

doi:10.1016/j.arcmed.2018.12.002

Cited by 22 publications

(14 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CKAP4 is an abundant type II transmembrane protein predominantly located in the endoplasmic reticulum and is implicated in regulating diverse biological activities in cells. 30 A recent study showed that CKAP4 was decreased in primary VSMCs of patients with AAA and contributed to the apoptosis arrest by the CDR1as/ CKAP4, cytoskeleton-associated protein 4 miR-7/CKAP4 axis. 31 In the present study, we also showed a decreased CKAP4 level in patients with AAA -a series of rescue experiments suggested that CKAP4 overexpression abolished the suppressing effects of the miR-545-3p inhibitor on VSMCs growth.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Circular RNA suppression of vascular smooth muscle apoptosis through the miR-545-3p/CKAP4 axis during abdominal aortic aneurysm formation

2023

View full text Add to dashboard Cite

Background: Abdominal aortic aneurysms (AAA) are an important cause of cardiovascular deaths. The loss of vascular smooth muscle cells (VSMCs) has been reported to be related to the pathology of AAA. This study focused on investigating the function of circ_0002168 in VSMC apoptosis. Methods: Levels of genes and proteins were measured by quantitative real-time-polymerase chain reaction (qRT-PCR) and Western blot. The growth of VSMCs was determined by using cell counting kit-8 assay, 5-ethynyl-2′-deoxyuridine (EdU) assay, flow cytometry and the evaluation of caspase-3 activity analysis, reactive oxygen species (ROS) production as well as lactate dehydrogenase (LDH) activity. The binding between miR-545-3p and circ_0002168 or Cytoskeleton-associated protein 4 (CKAP4) was confirmed by bioinformatics analysis, dual-luciferase reporter, RNA immunoprecipitation, and pull-down assays. Results: Circ_0002168 decreased in the aortic tissues of patients with AAA. Functionally, ectopic overexpression of circ_0002168 dramatically induced proliferation and suppressed apoptosis in VSMCs. Mechanistically, circ_0002168 sequestered miR-545-3p to release CKAP4 expression via the ceRNA mechanism, indicating the circ_0002168/miR-545-3p/CKAP4 feedback loop in VSMCs. Increased miR-545-3p and a decreased CKAP4 expression were observed in patients with AAA. Rescue experiments showed that miR-545-3p reversed the protective effects of circ_0002168 on VSMC proliferation. Moreover, inhibition of miR-545-3p could restrain the apoptosis of VSMCs, which was abolished by CKAP4 silencing. Conclusion: Circ_0002168 has a protective effect on VSMC proliferation by regulating the miR-545-3p/CKAP4 axis, adding further understanding of the pathogenesis of AAA and a potential therapeutic approach in AAA management.

show abstract

Section: Discussionmentioning

confidence: 99%

RETRACTED: Circular RNA suppression of vascular smooth muscle apoptosis through the miR-545-3p/CKAP4 axis during abdominal aortic aneurysm formation

2023

View full text Add to dashboard Cite

show abstract

“…Tryptase can also affect fibroblasts. In particular, numerous studies suggest that tryptase can stimulate proliferation and collagen synthesis in fibroblasts of various origin [159][160][161][162][163][164][165][166][167][168], and there is substantial evidence that tryptase acts on fibroblasts through PAR-2, ERK1/2 and peroxisome proliferator-activated receptor-γ [160,[165][166][167][168]. It has also been shown that tryptase can induce chemokine synthesis in fibroblasts and promote fibroblast chemotaxis [169,170].…”

Section: Fibroblastsmentioning

confidence: 99%

The emerging role of mast cell proteases in asthma

Pejler

2019

Eur Respir J

View full text Add to dashboard Cite

It is now well established that mast cells (MCs) play a crucial role in asthma. This is supported by multiple lines of evidence, including both clinical studies and studies on MC-deficient mice. However, there is still only limited knowledge of the exact effector mechanism(s) by which MCs influence asthma pathology. MCs contain large amounts of secretory granules, which are filled with a variety of bioactive compounds including histamine, cytokines, lysosomal hydrolases, serglycin proteoglycans and a number of MC-restricted proteases. When MCs are activated, e.g. in response to IgE receptor cross-linking, the contents of their granules are released to the exterior and can cause a massive inflammatory reaction. The MC-restricted proteases include tryptases, chymases and carboxypeptidase A3, and these are expressed and stored at remarkably high levels. There is now emerging evidence supporting a prominent role of these enzymes in the pathology of asthma. Interestingly, however, the role of the MC-restricted proteases is multifaceted, encompassing both protective and detrimental activities. Here, the current knowledge of how the MC-restricted proteases impact on asthma is reviewed.

show abstract

“…A study of inflammatory bowel disease (IBD) found that tryptase promotes fibrosis by activating the PAR-2/Akt/mTOR pathway of fibroblasts [ 75 ]. Meanwhile, there are reports about the role of the PI3K/Akt/ROCK pathway in pulmonary fibrosis and the PAR-2 and PAR γ pathways in atrial fibrosis [ 88 , 89 ]. Furthermore, tryptase can not only activate the mitosis and increase the migration activity of fibroblasts but also make them produce type I collagen fibronectin and laminin, which promote the formation of fibrosis [ 76 , 90 ].…”

Section: Pro-allergic and Inflammatory Actions Of Mcsmentioning

confidence: 99%

Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation

Zhang

Kurashima

2021

Cells

View full text Add to dashboard Cite

It is well known that mast cells (MCs) initiate type I allergic reactions and inflammation in a quick response to the various stimulants, including—but not limited to—allergens, pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs). MCs highly express receptors of these ligands and proteases (e.g., tryptase, chymase) and cytokines (TNF), and other granular components (e.g., histamine and serotonin) and aggravate the allergic reaction and inflammation. On the other hand, accumulated evidence has revealed that MCs also possess immune-regulatory functions, suppressing chronic inflammation and allergic reactions on some occasions. IL-2 and IL-10 released from MCs inhibit excessive immune responses. Recently, it has been revealed that allergen immunotherapy modulates the function of MCs from their allergic function to their regulatory function to suppress allergic reactions. This evidence suggests the possibility that manipulation of MCs functions will result in a novel approach to the treatment of various MCs-mediated diseases.

show abstract

Tryptase Promotes the Profibrotic Phenotype Transfer of Atrial Fibroblasts by PAR2 and PPARγ Pathway

Cited by 22 publications

References 37 publications

RETRACTED: Circular RNA suppression of vascular smooth muscle apoptosis through the miR-545-3p/CKAP4 axis during abdominal aortic aneurysm formation

RETRACTED: Circular RNA suppression of vascular smooth muscle apoptosis through the miR-545-3p/CKAP4 axis during abdominal aortic aneurysm formation

The emerging role of mast cell proteases in asthma

Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation

Contact Info

Product

Resources

About