[Effect of peroxisome proliferator-activated receptor-gamma on proliferation of airway smooth muscle cells in mice with asthma].

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[Effect of peroxisome proliferator-activated receptor-gamma on proliferation of airway smooth muscle cells in mice with asthma].

Zhongguo Dang Dai Er Ke Za Zhi. 2013 Jul;15(7):583-7

Authors: Gu MX, Liu XC, Jiang L

Abstract
OBJECTIVE: To investigate the effects of peroxisome proliferator-activated receptor-gamma (PPAR?) agonist rosiglitazone on the expression of cyclin D1 in lung tissue, and the proliferation of airway smooth muscle cells (ASMCs) in mice with bronchial asthma.
METHODS: Thirty clean BALB/c mice were randomly divided into control group (n=10), asthma group (n=10), and rosiglitazone treatment group (n=10). A mouse model of asthma was established by ovalbumin (OVA) sensitization and challenge. The treatment group received rosiglitazone (5 mg/kg) by gavage 1 hour before each challenge and the control group received saline instead of OVA sensitization and challenge. Leukocytes and eosinophils in bronchoalveolar lavage fluid (BALF) were counted under a microscope. Airway structural changes were observed by hematoxylin-eosin staining. Protein and mRNA expression levels of cyclin D1 were measured by immunohistochemical staining and RT-PCR. Perimeter of the basement membrane (Pbm), total bronchial wall area (WAt), airway smooth muscle area (WAm), and number of nuclei in ASMCs (N) were determined using image analysis software, and WAt/Pbm, WAm/Pbm, and N/Pbm were calculated.
RESULTS: Compared with the control group, the asthma group showed significant increases in the total number of leukocytes and percentage of eosinophils in BALF, as well as in the mRNA and protein expression of cyclin D1, but changes in these indices were significantly reduced in the rosiglitazone treatment group (P<0.05). In addition, compared with the control group, the asthma group had significantly increased WAt/Pbm, WAm/Pbm, and N/Pbm, but rosiglitazone significantly decreased these ratios (P<0.05).
CONCLISONS: Rosiglitazone may delay the process of airway remodeling by inhibiting the proliferation of ASMCs, so it can be used for preventing and treating chronic asthma.

PMID: 23866284 [PubMed – in process]

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The effect of unilateral adrenalectomy on transformation of adrenal medullary chromaffin cells in vivo: a potential mechanism of asthma pathogenesis.

The effect of unilateral adrenalectomy on transformation of adrenal medullary chromaffin cells in vivo: a potential mechanism of asthma pathogenesis.

PLoS One. 2012;7(9):e44586

Authors: Hu CP, Zou YQ, Feng JT, Li XZ

Abstract
BACKGROUND: Decreased epinephrine (EPI) is an important underlying factor of bronchoconstriction in asthma. Exogenous ?(2)-adrenergic receptor agonist is one of the preferred options to treat asthma. We previously showed that this phenomenon involved adrenal medullary chromaffin cell (AMCC) transformation to a neuron phenotype. However, the underlying molecular mechanism is not fully understood. To further explore this, an asthmatic model with unilateral adrenalectomy was established in this study.
METHODOLOGY/PRINCIPAL FINDINGS: Thirty-two rats were randomly into four groups (n?=?8 each) control rats (controls), unilateral adrenalectomy rats (surgery-control, s-control), asthmatic rats (asthma), unilateral adrenalectomy asthmatic rats (surgery-induced asthma, s-asthma). Asthmatic rats and s-asthmatic rats were sensitized and challenged with ovalbumin (OVA). The pathological changes in adrenal medulla tissues were observed under microscopy. EPI and its rate-limiting enzyme, phenylethanolamine N-methyl transferase (PNMT), were measured. Peripherin, a type III intermediate filament protein, was also detected in each group. The asthmatic rats presented with decreased chromaffin granules and swollen mitochondria in AMCCs, and the s-asthmatic rats presented more serious pathological changes than those in asthmatic rats and s-control rats. The expressions of EPI and PNMT in asthmatic rats were significantly decreased, as compared with levels in controls (P<0.05), and a further decline was observed in s-asthmatic rats (P<0.05). The expression of peripherin was higher in the asthmatic rats than in the controls, and the highest level was found in the s-asthmatic rats (P<0.05).
CONCLUSION/SIGNIFICANCE: Compared with asthmatic rats and s-control rats, the transformation tendency of AMCCs to neurons is more obvious in the s-asthmatic rats. Moreover, this phenotype alteration in the asthmatic rats is accompanied by reduced EPI and PNMT, and increased peripherin expression. This result provides further evidence to support the notion that phenotype alteration of AMCCs contributes to asthma pathogenesis.

PMID: 22957086 [PubMed – in process]

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