Abstract Objective To study the expression level of cAMP response element-binding protein (CREB) in children with recurrent wheezing under three years of age and its effect on the expression of the serum orosomucoid 1-like protein 3 (ORMDL3) gene. Methods Thirty-six children with recurrent wheezing under three years of age who visited the hospital from June 2017 to June 2019 were selected as the recurrent wheezing group. Twenty-four healthy children from physical examination were selected as the control group. The CREB expression level in peripheral blood was measured by quantitative real-time PCR. Human bronchial epithelial cells (BEAS-2B) were cultured, and dual-luciferase reporter assay and quantitative real-time PCR were used to investigate the effects of overexpression and siRNA interference of CREB on the promoter activity and mRNA expression of the ORMDL3 gene in the BEAS-2B cells. Results The expression level of CREB in the recurrent wheezing group was significantly higher than that in the control group (P < 0.001). In BEAS-2B cells, overexpression of CREB significantly up-regulated the promoter activity and mRNA expression of the ORMDL3 gene (P < 0.05), while siRNA interference of CREB significantly reduced the promoter activity and mRNA expression of the ORMDL3 gene (P < 0.05). Conclusions The expression of CREB is increased in children with recurrent wheezing, and CREB may be involved in the pathogenesis of recurrent wheezing by regulating expression of the ORMDL3 gene.
JIN Rui,ZHANG Zhen-Xing,ZHU Liang-Hua et al. Expression of CREB in children with recurrent wheezing and its effect on ORMDL3 gene expression[J]. CJCP, 2020, 22(9): 980-983.
JIN Rui,ZHANG Zhen-Xing,ZHU Liang-Hua et al. Expression of CREB in children with recurrent wheezing and its effect on ORMDL3 gene expression[J]. CJCP, 2020, 22(9): 980-983.
Akinbami LJ, Simon AE, Schoendorf KC. Trends in allergy prevalence among children aged 0-17 years by asthma status, United States, 2001-2013[J]. J Asthma, 2016, 53(4):356-362.
Zhang Y, Willis-Owen SAG, Spiegel S, et al. The ORMDL3 asthma gene regulates ICAM1 and has multiple effects on cellular inflammation[J]. Am J Respir Crit Care Med, 2019, 199(4):478-488.
Schedel M, Michel S, Gaertner VD, et al. Polymorphisms related to ORMDL3 are associated with asthma susceptibility, alterations in transcriptional regulation of ORMDL3, and changes in TH2 cytokine levels[J]. J Allergy Clin Immunol, 2015, 136(4):893-903.e14.
[6]
金蕊. 人ORMDL3基因的转录调控研究[D]. 南京:南京医科大学, 2012.
[7]
Andrews CS, Miyata M, Susuki-Miyata S, et al. Nontypeable haemophilus influenzae-induced MyD88 short expression is regulated by positive IKKβ and CREB pathways and negative ERK1/2 pathway[J]. PLoS One, 2015, 10(12):e0144840.
[8]
Wang Y, Ma H, Tao X, et al. SCF promotes the production of IL-13 via the MEK-ERK-CREB signaling pathway in mast cells[J]. Exp Ther Med, 2019, 18(4):2491-2496.
[9]
Liao YP, Du WM, Hu Y, et al. CREB/Wnt10b mediates the effect of COX-2 on promoting BMP9-induced osteogenic differentiation via reducing adipogenic differentiation in mesenchymal stem cells[J]. J Cell Biochem, 2019, 120(6):9572-9587.
[10]
Barátki BL, Huber K, Sármay G, et al. Inflammatory signal induced IL-10 production of marginal zone B-cells depends on CREB[J]. Immunol Lett, 2019, 212:14-21.
[11]
Bostik P, Noble ES, Stephenson ST, et al. CD4+ T cells from simian immunodeficiency virus disease-resistant sooty mangabeys produce more IL-2 than cells from disease-susceptible species:involvement of p300 and CREB at the proximal IL-2 promoter in IL-2 up-regulation[J]. J Immunol, 2007, 178(12):7720-7729.
[12]
Koga Y, Hisada T, Ishizuka T, et al. CREB regulates TNF-α-induced GM-CSF secretion via p38 MAPK in human lung fibroblasts[J]. Allergol Int, 2016, 65(4):406-413.
[13]
Kim D, Cho S, Woo JA, et al. A CREB-mediated increase in miRNA let-7f during prolonged β-agonist exposure:a novel mechanism of β2-adrenergic receptor down-regulation in airway smooth muscle[J]. FASEB J, 2018, 32(7):3680-3688.
[14]
Avsar B, Zhao Y, Li W, et al. Atropa belladonna expresses a microRNA (aba-miRNA-9497) highly homologous to homo sapiens miRNA-378(hsa-miRNA-378); both miRNAs target the 3'-untranslated region (3'-UTR) of the mRNA encoding the neurologically relevant, zinc-finger transcription factor ZNF-691[J]. Cell Mol Neurobiol, 2020, 40(1):179-188.
