Effects of exposure to cigarette smoke on expression of Wnt3a and β-catenin protein in rat lung tissue

( views:149, downloads:0 )
ZOU Wei-feng(State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical College, Guangzhou 510120,China)
HU Guo-pin(State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical College, Guangzhou 510120,China)
LI Bing()
RAN Pi-xin()
Journal Title:
Chinese Journal of Biomedical Engineering
Volume 18, Issue 01, 2012
Key Word:
Pulmonary disease,chronic obstructive;Wnt proteins;Wnt-β-catenin signaling pathway;Airway remodeling;Cigarette smoke;Rats

Abstract: Objective To investigate the effects of cigarette smoke(CS) exposure on expression of Wnt3a and β-catenin protein in rat lung tissue.Methods Twenty female SD rats were allocated to 2 groups (n=10 each) by random digit table:the control group and CS exposure group(model group).Rats in model group were subjected to twice-daily 45-min CS exposure,while the rats in control group were kept isolated from CS.The animals were sacrificed on day 100 to be harvested for lung tissues which were then studied for pathological morphology under light microscopy,expressions of α-smooth muscle actin (α-SMA),Wnt3a and β-catenin proteins by immunohistochemistry, and thickness of bronchial smooth muscle layer by morphometry.Results The rats in model group showed chronic inflammation,emphysema-like change and thickening of small airway walls and smooth muscle layers in the lung tissues.In both groups,α-SMA protein was localized in the smooth muscle layer of airway and vessel.The mean thickness of bronchial smooth muscle was significantly greater in the model group than those in control group [ (3.06±0.62) μm vs ( 1.86±0.43) μm,P<0.05].Wnt3a and β-catenin were mainly expressed in the bronchial and alveolar epithelium.In model group and control group,the levels of Wnt3a expression were 74.54 ±4.14 vs 89.24 ± 3.02 in bronchial epithelial cells,and 91.97 ± 2.50 vs 110.46 ± 3.85 in alveolar epithelial cells,with significant differences between groups (both P<0.05) ; the levels of β-catenin expression were 86.97±4.87 vs 103.18±3.77 in cytoplasm of bronchial epithelial cells,and 95.75 ±3.91 vs 116.12±5.76 in nuclei of bronchial epithelial cells,106.24±4.57 vs 128.81±3.96 in cytoplasm of alveolar epithelial cells,and 125.44±4.89 vs 152.90±4.10 in nuclei of alveolar epithelial cells,with significant differences between groups (all P<0.05).Conclusions Cigarette smoke may induce up-regulation of Wnt3a and β-catenin proteins in rat lung tissue.

  • [1]Chilosi M,Poletti V,Zamò A,et al.Aberrant Wnt/beta-catenin pathway activation in idiopathic pulmonary fibrosis. Am J Pathol,2003,162:1495-1502.
  • [2]Cohen ED,Ihida-Stansbury K,Lu MM,et al.Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.J Clin Invest,2009,119:2538-2549.
  • [3]Suzuki M,Wada H,Yoshino M,et al.Molecular characterization of chronic obstructive pulmonary disease-related non-small cell lung cancer through aberrant methylation and alterations of EGFR signaling.Ann Surg Oncol,2010,17:878-888.
  • [4]Lemjabbar-Alaoui H,Dasari V,Sidhu SS,et al.Wnt and Hedgehog are critical mediators of cigarette smoke-induced lung cancer.PLoS One,2006,1:e93.
  • [5]Cosio M,Ghezzo H,Hogg JC,et al.The relations between structural changes in small airways and pulmonary-function tests.N Engl J Med,1978,298:1277-1281.
  • [6]Bai A,Eidelman DH,Hogg JC,et al.Proposed nomenclature for quantifying Subdivisions of the bronchial wall.J Appl Physiol,1994,77:1011-1014.
  • [7]中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2007年修订版).中华结核和呼吸杂志,2007,30:8-17.
  • [8]Nelson WJ,Nusse R.Convergence of Wnt,beta-catenin,and cadherin pathways.Science,2004,303:1483-1487.
  • [9]Metzger RJ,Klein OD,Martin GR,et al.The branching programme of mouse lung development.Nature,2008,453:745-750.
  • [10]Iwano M,Plieth D,Danoff TM,et al.Evidence that fibroblasts derive from epithelium during tissue fibrosis.J Clin Invest,2002,110:341-350.
  • [11]Kim K,Lu Z,Hay ED.Direct evidence for a role of betacatenin/LEF-1 signaling pathway in induction of EMT.Cell Biol Int,2002,26:463-476.
  • [12]Masszi A,Fan L,Rosivall L,et al.Integrity of cell-cell contacts is a critical regulator of TGF-beta 1-induced epithelial-to-myofibroblast transition:role for beta-catenin.Am J Pathol,2004,165:1955-1967.
  • [13]K(o)nigshoff M,Balsara N,Pfaff EM,et al.Functional Wnt signaling is increased in idiopathic pulmonary fibrosis.PLoS One,2008,3:e2142.
  • [14]Lu W,Yamamoto V,Ortega B,et al.Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth.Cell,2004,119:97-108.
  • [15]Sohal SS, Reid D, Soltani A, et al.Reticular basement membrane fragmentation and potential epithelial mesenchymal transition is exaggerated in the airways of smokers with chronic obstructive pulmonary disease.Respirology,2010,15:930-938.
  • [16]Schmidt M, Sun G, Stacey MA, et al.Identification of circulating fibrocytes as precursors of bronchial myofibroblasts in asthma.J Immunol,2003,171:380-389.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615 Email:yiyao@wanfangdata.com.cn