Abstract OBJECTIVE: To investigate the effects of peroxisome proliferator-activated receptor-gamma (PPARγ) 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.
GU Ming-Xiao,LIU Xuan-Cheng,JIANG Lu. Effect of peroxisome proliferator-activated receptor-gamma on proliferation of airway smooth muscle cells in mice with asthma[J]. CJCP, 2013, 15(7): 583-587.
GU Ming-Xiao,LIU Xuan-Cheng,JIANG Lu. Effect of peroxisome proliferator-activated receptor-gamma on proliferation of airway smooth muscle cells in mice with asthma[J]. CJCP, 2013, 15(7): 583-587.
[1]Fahy JY, Corry DB, Boushey HA. Airway inflammation and remodeling in asthma[J]. Curt Opin Plllm Med, 2000, 6(1): 15-20.
[2]Mcmillan SJ, Xanthou G, Lloyd CM. Manipulation of allergen-induced airway remedeling by treatment with anti-TGF-β antibody: effect on the Smad signaling pathway[J]. J Immunol, 2005, 174(9):5774-5780.
[3]Lee KS, Park SJ, Hwang PH, Yi HK, Song CH, Chai OH, et al. PPAR-7 modulates allcrgic inflammation through up-regulation of PTEN[J]. FASEB J, 2005, 19(8): 1033-1035.
[4]Honda K, Marquillies P, Capron M, Dombrowicz D. Peroxisome prolifemtor-activated receptor T is expressed in airways and inhibits features of airway remodeling in amouse asthma model[J]. J Allergy Clin Immunol, 2004, 113(5): 882-888.
[5]Kips JC, Anderson GP, Fredberg JJ, Herz U, Inman MD, Jordana M,et al. Murine models of asthma[J]. Eur Respir J, 2003, 22(2): 374-382.
[7]Tliba O, Amrani Y, Panettieri RA. Is airway smooth muscle the “missing link” modulating airway inflammation in asthma?[J]. Chest, 2008, 133(1): 236-242.
[8]Pelaia G, Renda T, Gallelli L. Molecular mechanisms underlying airway smooth muscle contraction and proliferation: implications for asthma[J]. Respir Med, 2008, 102(8): 1173-1181.
[9]Gosens R, Roscioni SS, Dekkers BG, Pera T, Schmidt M, Schaafsma D, et al. Pharmacology of airway smooth muscle proliferation[J]. Eur J Pharmacol, 2008, 585(2-3):385-397.
[10]Ward JE, Gould H, Harris T, Bonacci JV, Stewart AG. PPAR gamma ligands, 15-deoxy-delta12, 14-prostaglandin J2 and rosiglitazone regulate human cultured airway smooth muscle proliferation through different mechanisms[J]. Br J Pharmacol, 2004, 141(3): 517-525.
[11]Qiu LQ, Sinniah R, Hsu SI. Role of differential and cell typespecific expression of cell cycle regulatory proteins in mediating progressive glomerular injury in human IgA[J]. Nephropathy Lab Invest, 2004, 84(9): 1112-1125.
[12]Ueno T, Teraoka N, Takasu S, Nakano K, Takahashi M, Yamamoto M, et al. Suppressive effect of Pioglitazone, a PPAR gamma ligand, on azoxymethane-induced colon aberrant crypt foci in KK-Ay Mice[J]. Asian Pac J Cancer Prev, 2012, 13(8): 4067-7403.