[Cyclin D1 and its association with airway remodeling in a murine model of asthma].
OBJECTIVE
To evaluate the expression of cyclin D(1) in asthmatic mouse lungs, and to explore the role of cyclin D(1) in bronchial asthma and airway remodeling.


METHODS
Forty BALB/c mice were randomized to group A (normal), group B (sensitized for 2 weeks), group C (sensitized for 4 weeks) and group D (sensitized for 8 weeks), 10 mice each group. The mice were sensitized with 10% ovalbumin and challenged with 1% ovalbumin to establish the asthmatic model. The number of eosinophils and the cell percentages in bronchoalveolar lavage fluid (BALF) were counted by cytology method. Pulmonary functions were measured to evaluate the resistance of expiration. Airway inflammation and eosinophil infiltration were evaluated by HE staining, and the airway wall thickness (WAt/Pi), smooth muscle thickness (WAm/Pi) and smooth nucleus counts (N/Pi) were quantified by computer-assisted image analysis system. The mRNA expression of cyclin D(1) was measured by RT-PCR and Real-time PCR. The protein expression of cyclin D(1) was assayed by Western blot. The correlation between airway resistance of expiration and the expression of cyclin D(1) was studied.


RESULTS
The eosinophil count and differential in BALF of group B, C, and D [(42.6 +/- 0.9) x 10(4)/L, (54.7 +/- 1.4) x 10(4)/L, (44.8 +/- 2.4) x 10(4)/L] were higher than those of group A (3.4 +/- 0.5) x 10(4)/L (q = 79.75, 91.42, 84.82, all P < 0.01). The airway resistance of expiration after challenge with 45 microg/kg acetylcholine in group B, C, and D [(5.27 +/- 0.16) cmxL(-1)xmin(-1), (6.68 +/- 0.20) cmxL(-1)xmin(-1), (7.14 +/- 0.41) cmxL(-1)xmin(-1)] was higher than that in group A [(4.11 +/- 0.15) cmxL(-1)xmin(-1), q = 5.58, 6.39, 7.11, all P < 0.05]. Eosinophil infiltration, cilium loss, formation of mucus plug and smooth muscle cell layer thickening were observed in group B, C, and D. The morphological changes of the airways became evident following airway remodeling. WAm/Pi in group B, C, and D (2.8 +/- 0.6, 4.8 +/- 0.6, 6.4 +/- 0.7) were higher than in group A (2.4 +/- 0.4, q = 6.40, 8.28, 9.27, all P < 0.05), and WAt/Pi in group B, C, and D (6.4 +/- 0.8, 8.3 +/- 1.2, 9.3 +/- 1.0) were higher than in group A (5.6 +/- 1.0, q = 2.80, 4.83, 6.37, all P < 0.05). The protein expression of Cyclin D(1) in group B, C, and D (0.587 +/- 0.015, 0.808 +/- 0.029, 0.826 +/- 0.022) were higher than in group A (0.404 +/- 0.016, q = 5.87, 8.08, 8.26, all P < 0.01). There was a positive correlation between the expression of cyclin D(1) and airway resistance (r = 0.83, P < 0.05).


CONCLUSIONS
The expression of cyclin D(1) in the asthmatic mouse lung was increased, and positively correlated to airway reactivity. Cyclin D(1) might be essential in the airway remodeling of asthma through ERK signaling pathway.
Ge
Hai-yan
HY
Department of Respiratory Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Huang
Mao
M
Yao
Xin
X
Yin
Kai-sheng
KS
Yang
Yu
Y
D056151:Airway Remodeling; D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology*; D019938:Cyclin D1 / Q000378:metabolism*; D004804:Eosinophils; D005260:Female; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C
C530105:Ccnd1 protein, mouse; D019938:Cyclin D1