Differential expression of peroxisome proliferator activated receptor γ and cyclin D1 does not affect proliferation of asthma‐ and non‐asthma‐derived airway smooth muscle cells

Lau, Justine Y; Oliver, Brian G.; Moir, Lyn M.; Black, Judith L.; Burgess, Janette K.

doi:10.1111/j.1440-1843.2009.01683.x

Cited by 9 publications

(11 citation statements)

References 27 publications

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“…Consistent with the reported antiproliferative effects of PPAR γ ligands on human ASM in vitro [18, 50, 55], intranasal administration of CGZ has been shown to reduce not only eosinophilic inflammation, but also to inhibit the thickening of the ASM layer following allergen challenge [95]. This effect appeared to be independent of regulation of TGF β or VEGF levels, as the increased BAL levels of these potential mitogens were not reduced with CGZ treatment [95].…”

Section: In Vivo Regulation Of Asm Function By Pparγ Ligandssupporting

confidence: 53%

“…In the same study, asthmatics treated with GCS had lower levels of PPAR γ expression compared with untreated asthmatics. Although ASM from asthmatics had lower PPAR γ levels compared to healthy controls in vitro , this was reversed in the presence of a mitogenic stimulus [50]. These results suggest that increased PPAR γ expression observed in situ may be a product of the inflammatory and mitogenic pathways and may also be sensitive to steroid therapy.…”

Section: Pparγ Is Increased In Airway Smooth Muscle In Asthmamentioning

confidence: 99%

“…Since GCS can only inhibit the in vitro proliferation of ASM from subjects without asthma [68, 71], alternative therapeutic approaches are required to target this steroid-resistant mitogenic response. In a recent study, the effects of CGZ were assessed in cells from nonasthmatic and asthmatic patients cellular proliferation in response to serum by measuring bromodeoxyuridine uptake [50]. Further studies are required to explain why CGZ failed to inhibit serum-induced proliferation in either group [50], since this finding contradicts the previously reported antiproliferative effects of both CGZ [55] and RGZ [18].…”

Section: In Vitro Regulation Of Asm Function By Pparγ Ligandsmentioning

confidence: 99%

“…In a recent study, the effects of CGZ were assessed in cells from nonasthmatic and asthmatic patients cellular proliferation in response to serum by measuring bromodeoxyuridine uptake [50]. Further studies are required to explain why CGZ failed to inhibit serum-induced proliferation in either group [50], since this finding contradicts the previously reported antiproliferative effects of both CGZ [55] and RGZ [18]. CGZ did upregulate PPAR γ expression in ASM cells derived from both asthmatic and nonasthmatic subjects, and in ASM from asthmatics in the presence of serum [50], however the functional significance of these changes and their potential impact on ASM in remodeled airways remain to be determined.…”

Section: In Vitro Regulation Of Asm Function By Pparγ Ligandsmentioning

confidence: 99%

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

2012

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In asthma, the increase in airway smooth muscle (ASM) can contribute to inflammation, airway wall remodeling and airway hyperresponsiveness (AHR). Targetting peroxisome proliferator-activated receptor γ (PPARγ), a receptor upregulated in ASM in asthmatic airways, may provide a novel approach to regulate these contributions. This review summarises experimental evidence that PPARγ ligands, such as rosiglitazone (RGZ) and pioglitazone (PGZ), inhibit proliferation and inflammatory cytokine production from ASM in vitro. In addition, inhaled administration of these ligands reduces inflammatory cell infiltration and airway remodelling in mouse models of allergen-induced airways disease. PPARγ ligands can also regulate ASM contractility, with acute treatment eliciting relaxation of mouse trachea in vitro through a PPARγ-independent mechanism. Chronic treatment can protect against the loss of bronchodilator sensitivity to β 2-adrenoceptor agonists and inhibit the development of AHR associated with exposure to nicotine in utero or 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 PPARγ agonists to target the noncontractile and contractile functions of ASM to improve outcomes for patients with poorly controlled asthma.

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Section: In Vivo Regulation Of Asm Function By Pparγ Ligandssupporting

confidence: 53%

Section: Pparγ Is Increased In Airway Smooth Muscle In Asthmamentioning

confidence: 99%

Section: In Vitro Regulation Of Asm Function By Pparγ Ligandsmentioning

confidence: 99%

Section: In Vitro Regulation Of Asm Function By Pparγ Ligandsmentioning

confidence: 99%

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

2012

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“…Cyclin D1 has been the most widely studied cyclin in ASM biology using cells from nonasthmatics [4, 9, 10] and more recently asthmatics [11]. Our study examines cyclin D1 mRNA and protein expression in ASM cells from asthmatics and demonstrates that cyclin D1 upregulation is insensitive to corticosteroid inhibition.…”

Section: Introductionmentioning

confidence: 93%

Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition

et al. 2012

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Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G1 cell cycle progression—cyclin D1—in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

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Airway Smooth Muscle Dysfunction in Asthma

Koziol‐White

Panettieri

2022

Encyclopedia of Respiratory Medicine

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Differential expression of peroxisome proliferator activated receptor γ and cyclin D1 does not affect proliferation of asthma‐ and non‐asthma‐derived airway smooth muscle cells

Abstract: Although in the presence of a mitogenic stimulus, PPARgamma was differentially expressed in asthma- and non-asthma-derived ASM; its expression was not related to the increased proliferation observed in asthmatic ASM.

Cited by 9 publications

References 27 publications

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

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

Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition

Airway Smooth Muscle Dysfunction in Asthma

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