Effect of Peroxisome Proliferator-Activated Receptor-Gamma on Airway Smooth Muscle Thickening in a Murine Model of Chronic Asthma

2008 ◽  
Vol 148 (4) ◽  
pp. 289-296 ◽  
Author(s):  
Chin Kook Rhee ◽  
Sook Young Lee ◽  
Ji Young Kang ◽  
Seung Joon Kim ◽  
Soon Suk Kwon ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Murine Model ◽  
Peroxisome Proliferator ◽  
Chronic Asthma ◽  
Peroxisome Proliferator Activated Receptor

Inhaled corticosteroid prevents the thickening of airway smooth muscle in murine model of chronic asthma

2008 ◽  
Vol 21 (1) ◽  
pp. 14-19 ◽  
Author(s):  
Sook Young Lee ◽  
Jin Sook Kim ◽  
Jung Mi Lee ◽  
Soon Seok Kwon ◽  
Kwan Hyung Kim ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Murine Model ◽  
Chronic Asthma ◽  
Inhaled Corticosteroid

scholarly journals PPARγLigands Regulate Noncontractile and Contractile Functions of Airway Smooth Muscle: Implications for Asthma Therapy

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Chantal Donovan ◽  
Xiahui Tan ◽  
Jane Elizabeth Bourke
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Allergen Challenge ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Cytokine Production ◽  
Novel Approach ◽  
Independent Mechanism ◽  
Adrenoceptor Agonists

In asthma, the increase in airway smooth muscle (ASM) can contribute to inflammation, airway wall remodeling and airway hyperresponsiveness (AHR). Targetting peroxisome proliferator-activated receptorγ(PPARγ), a receptor upregulated in ASM in asthmatic airways, may provide a novel approach to regulate these contributions. This review summarises experimental evidence that PPARγligands, such as rosiglitazone (RGZ) and pioglitazone (PGZ), inhibit proliferation and inflammatory cytokine production from ASMin vitro. In addition, inhaled administration of these ligands reduces inflammatory cell infiltration and airway remodelling in mouse models of allergen-induced airways disease. PPARγligands can also regulate ASM contractility, with acute treatment eliciting relaxation of mouse tracheain vitrothrough a PPARγ-independent mechanism. Chronic treatment can protect against the loss of bronchodilator sensitivity toβ2-adrenoceptor agonists and inhibit the development of AHR associated with exposure to nicotinein uteroor following allergen challenge. Of particular interest, a small clinical trial has shown that oral RGZ treatment improves lung function in smokers with asthma, a group that is generally unresponsive to conventional steroid treatment. These combined findings support further investigation of the potential for PPARγagonists to target the noncontractile and contractile functions of ASM to improve outcomes for patients with poorly controlled asthma.

scholarly journals IgE Downregulates PTEN through MicroRNA-21-5p and Stimulates Airway Smooth Muscle Cell Remodeling

2019 ◽  
Vol 20 (4) ◽  
pp. 875 ◽  
Author(s):  
Lei Fang ◽  
Xinggang Wang ◽  
Qingzhu Sun ◽  
Eleni Papakonstantinou ◽  
Chongteck S’ng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Allergic Asthma ◽  
Airway Smooth Muscle ◽  
Muscle Cell ◽  
Airway Smooth Muscle Cell ◽  
Mitochondrial Activity ◽  
Peroxisome Proliferator ◽  
Airway Wall ◽  
Peroxisome Proliferator Activated Receptor

The patho-mechanism leading to airway wall remodeling in allergic asthma is not well understood and remodeling is resistant to therapies. This study assessed the effect of immunoglobulin E (IgE) in the absence of allergens on human primary airway smooth muscle cell (ASMC) remodeling in vitro. ASMCs were obtained from five allergic asthma patients and five controls. Proliferation was determined by direct cell counts, mitochondrial activity by expression of cytochrome c, protein expression by immunoblotting and immuno-fluorescence, cell migration by microscopy imaging, and collagen deposition by cell based ELISA and RNA expression by real time PCR. Non-immune IgE activated two signaling pathways: (i) signal transducer and activator of transcription 3 (STAT3)→miR-21-5p→downregulating phosphatase and tensin homolog (PTEN) expression, and (ii) phosphatidylinositol 3-kinases (PI3K)→protein kinase B (Akt)→mammalian target of rapamycin (mTOR)→ribosomal protein S6 kinase beta-1 (p70s6k)→peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1-α)→peroxisome proliferator-activated receptor-γ (PPAR-γ)→cyclooxygenase-2 (COX-2)→mitochondrial activity, proliferation, migration, and extracellular matrix deposition. Reduced PTEN expression correlated with enhanced PI3K signaling, which upregulated ASMC remodeling. The inhibition of microRNA-21-5p increased PTEN and reduced mTOR signaling and remodeling. Mimics of microRNA-21-5p had opposing effects. IgE induced ASMC remodeling was significantly reduced by inhibition of mTOR or STAT3. In conclusion, non-immune IgE alone is sufficient for stimulated ASMC remodeling by upregulating microRNA-21-5p. Our findings suggest that the suppression of micoRNA-21-5p may present a therapeutic target to reduce airway wall remodeling.

Effect of Imatinib on Airway Smooth Muscle Thickening in a Murine Model of Chronic Asthma

2011 ◽  
Vol 155 (3) ◽  
pp. 243-251 ◽  
Author(s):  
Chin Kook Rhee ◽  
Jin Woo Kim ◽  
Chan Kwon Park ◽  
Joo Sang Kim ◽  
Ji Young Kang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Murine Model ◽  
Chronic Asthma

scholarly journals Effect of Salusin-ß on Peroxisome Proliferator-Activated Receptor Gamma Gene Expression in Vascular Smooth Muscle Cells and its Possible Mechanism

2015 ◽  
Vol 36 (6) ◽  
pp. 2466-2479 ◽  
Author(s):  
XiaoLe Xu ◽  
Mengzi He ◽  
Tingting Liu ◽  
Yi Zeng ◽  
Wei Zhang
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Nuclear Translocation ◽  
Muscle Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Gene

Background/Aims: salusin-ß is considered to be a potential pro-atherosclerotic factor. Regulation and function of vascular smooth muscle cells (VSMCs) are important in the progression of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ) exerts a vascular protective role beyond its metabolic effects. Salusin-ß has direct effects on VSMCs. The aim of the present study was to assess the effect of salusin-ß on PPARγ gene expression in primary cultured rat VSMCs. Methods: Western blotting analysis, real-time PCR and transient transfection approach were used to determine expression of target proteins. Specific protein knockdown was performed with siRNA transfection. Cell proliferation was determined by 5-bromo-2'-deoxyuridine incorporation. The levels of inflammation indicators interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) were determined using enzyme-linked immunosorbent assay. Results: Salusin-ß negatively regulated PPARγ gene expression at protein, mRNA and gene promoter level in VSMCs. The inhibitory effect of salusin-ß on PPARγ gene expression contributed to salusin-ß-induced VSMCs proliferation and inflammation in vitro. IγBa-NF-γB activation, but not NF-γB p50 or p65, mediated the salusin-ß-induced inhibition of PPARγ gene expression. Salusin-ß induced nuclear translocation of histone deacetylase 3 (HDAC3). HDAC3 siRNA prevented salusin-ß-induced PPARγ reduction. Nuclear translocation of HDAC3 in response to salusin-ß was significantly reversed by an IγBa inhibitor BAY 11-7085. Furthermore, IγBa-HDAC3 complex was present in the cytosol of VSMCs but interrupted after salusin-ß treatment. Conclusion: IγBa-HDAC3 pathway may contribute to salusin-ß-induced inhibition of PPARγ gene expression in VSMCs.

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