Abstract：Objective To investigate the effect of KyoT2 on the proliferation and migration of airway smooth muscle cells (ASMCs) in mice with asthma. Methods Ovalbumin (OVA) was used to establish the asthmatic model of airway remodeling in BALB/c mice. ASMCs were isolated and cultured, and primarily cultured ASMCs were used as the control group. The expression of KyoT2 in ASMCs was measured in the control and asthma groups. After the ASMCs from asthmatic mice were transfected with pCMV-Myc (empty vector group) or pCMV-Myc-KyoT2 plasmid with overexpressed KyoT2 (KyoT2 expression group) for 48 hours, RT-PCR and Western blot were used to measure the mRNA and protein expression of KyoT2, the MTT assay and BrdU assay were used to measure the proliferation of ASMCs, and Transwell assay was used to measure the migration of ASMCs. Western blot was used to determine the effect of KyoT2 overexpression on the protein expression of RBP-Jκ, PTEN, and AKT. Results Compared with the control group, the asthma group had significantly downregulated expression of KyoT2 in ASMCs, and the KyoT2 expression group had significantly upregulated expression of KyoT2 in ASMCs (P < 0.05). Compared with the empty vector group, overexpressed KyoT2 significantly inhibited cell proliferation and migration, downregulated the expression of RBP-Jκ and AKT, and upregulated the expression of PTEN. Conclusions Overexpressed KyoT2 can inhibit the proliferation and migration of ASMCs through the negative regulation of RBP-Jκ/PTEN/AKT signaling pathway.
ZHAO Long,LIU Cui-Cui,SHI Xiao-Lan et al. Inhibitory effect of KyoT2 overexpression on proliferation and migration of airway smooth muscle cells in mice with asthma[J]. CJCP, 2016, 18(9): 885-890.
To T, Stanojevic S, Moores G, et al. Global asthma prevalence in adults:findings from the cross-sectional world health survey[J]. BMC Public Health, 2012, 12:204.
[2]
Gasana J, Dillikar D, Mendy A, et al. Motor vehicle air pollution and asthma in children:a meta-analysis[J]. Environ Res, 2012, 117:36-45.
Hu M, Ou-Yang HF, Han XP, et al. KyoT2 downregulates airway remodeling in asthma[J]. Int J Clin Exp Pathol, 2015, 8(11):14171-14179.
[5]
Li LH, Lu B, Wu HK, et al. Apigenin inhibits TGF-β1-induced proliferation and migration of airway smooth muscle cells[J]. Int J Clin Exp Pathol, 2015, 8(10):12557-12563.
[6]
Hamelmann E, Schwarze J, Takeda K, et al. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography[J]. Am J Respir Crit Care Med, 1997, 156(3 Pt 1):766-775.
[7]
Qin H, Wang J, Liang Y, et al. RING1 inhibits transactivation of RBP-J by Notch through interaction with LIM protein KyoT2[J]. Nucleic Acids Res, 2004, 32(4):1492-1501.
[8]
Whelan JT, Forbes SL, Bertrand FE. CBF-1(RBP-J kappa) binds to the PTEN promoter and regulates PTEN gene expression[J]. Cell Cycle, 2007, 6(1):80-84.
[9]
Von Mutius E. The microbial environment and its influence on asthma prevention in early life[J]. J Allergy Clin Immunol, 2016, 137(3):680-689.
[10]
Ozdogan S, Tabakci B, Demirel AS, et al. The evaluation of risk factors for recurrent hospitalizations resulting from wheezing attacks in preschool children[J]. Ital J Pediatr, 2015, 41:91.
[11]
Prakash YS. Airway smooth muscle in airway reactivity and remodeling:what have we learned[J]. Am J Physiol Lung Cell Mol Physiol, 2013, 305(12):L912-L933.
