Epithelium expression and function of retinoid receptors in asthma

被引：45

作者：

Druilhe, Anne ^{[1
]}

Zahm, Jean-Marie ^{[4
]}

Benayoun, Laurent ^{[1
]}

El Mehdi, Delphine ^{[1
]}

Grandsaigne, Martine ^{[1
]}

Dombret, Marie-Christine ^{[2
]}

Mosnier, Isabelle ^{[5
]}

Feger, Benoit ^{[6
]}

Depondt, Joeel ^{[3
]}

Aubier, Michel ^{[1
,2
]}

Pretolani, Marina ^{[1
]}

机构：

[1] Univ Paris 07, Fac Med Denis Diderot, Inserm, U700, F-75018 Paris, France

[2] Grp Hosp Univ Nord Bichat Claude Bernard, AP HP, Serv Pneumol A, Paris, France

[3] Grp Hosp Univ Nord Bichat Claude Bernard, AP HP, Serv Otorhinolaryngol, Paris, France

[4] Univ Reims, CHU Reims, Hop Maison Blanche Reims, Inserm,U514, Reims, France

[5] Grp Hosp Univ Nord Beaujon, AP HP, Serv Otorhinolaryngol, Clichy, France

[6] Clin Pasteur, Brest, France

来源：

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY | 2008年 / 38卷 / 03期

关键词：

epithelium repair; airway remodeling; transforming-growth factor-beta; metalloproteinase-9;

D O I：

10.1165/rcmb.2006-0453OC

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Abnormal epithelial repair to damage participates in airway remodeling in asthma by the paracrine regulation of mesenchymal cell functions. Retinoids control epithelial functions through nuclear retinoic acid receptor (RAR) and retinoid X receptor (RXR) activation, yet their expression and contribution to epithelial repair and to airway remodeling in asthma are unknown. We determined the plasma levels of retinol and the immunohistochemical expression of retinoid receptors in damaged and repaired bronchial epithelium from 9 control subjects, 10 subjects with intermittent asthma, 8 subjects with mild-to-moderate asthma, and 8 subjects with severe asthma. In addition, the effect of the retinoid receptor ligands, all-trans-retinoic acid, and 9-cis retinoic acid, on the synthesis of 38 factors potentially involved in epithelial repair and in airway remodeling was determined in human cultured airway epithelial cells an correlated with cell migration and proliferation. Circulating retinol was similar in the three patient groups. In contrast, the epithelial expression of RAR gamma, RXR alpha, and RXR gamma was greater in subjects with severe asthma, as compared with patients with milder disease and to control subjects. Retinoid receptor expression correlated positively with the proportion of morphologically intact epithelium. In vitro, retinoids up-regulated the expression of the transcripts encoding transforming growth factor (TGF)-beta 1, metalloproteinase-9, beta 1-integrin, and hepatocyte growth factor receptor, and promoted wound repair and chemokinesis of human airway epithelial cells without altering proliferation. Cell treatment with an anti-TGF-beta 1 monoclonal antibody partially reduced retinoid-induced effects. Persistent interaction between retinoids and some of their receptors, which are overexpressed by the bronchial epithelium of individuals with severe asthma, may contribute to an abnormal repair and to airway remodeling, partly through TGF-beta 1 production.

引用

页码：276 / 282

页数：7

共 53 条

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