ABSTRACT
Asthma is a chronic inflammatory disease of the airway.Repeated inflammatory injury and tissue repair can lead to airway remodeling.The airway epithelial mesenchymal transformation (EMT) plays an important role in airway remodeling of asthma.Various cytokines and signaling pathways,such as transforming growth factor β (TGF-β),nuclear factor-kappa B (NF-κB) and bromodomain-containing protein 4 (BRD4),are involved in the molecular regulation of EMT.
ABSTRACT
Asthma is a chronic airway disease characterized by airway inflammation and airway remodeling. Chronic airway inflammation can be involved in airway remodeling in asthmatic patients by incuding epithelial-mesenchymal transition (EMT).Bromodomain-containing protein 4 (BRD4) is a key transcriptional regulator in mammals,and many evidences have shown that BRD4 plays a pivotal role in airway remodeling via nuclear factor-κB/RelA signaling pathway. This review summarizes the recent advances in the role of BRD4 in regulating EMT,with an attempt to elucidate the molecular mechanisms of asthma and inform the prevention and control of asthma.
ABSTRACT
Objective To explore the underlying mechanism of respiratory syncytial virus-related asthma .Methods Totally 30 sprague-dawley rats were randomly divided into control group ,respiratory syncytial virus (RSV) group ,and anti-NGF group ,with 10 in each group .RSV infection model was established by nasal drip once a week .In anti-NGF antibody intervention group ,each rat was given intraperitoneal injection of anti-NGF for 3 h before identical RSV infection .transmission electron microscopy(TEM) were performed to observe the ultramicro-structure changes in adrenal medullary cell .The concentrations of adrenaline and NGF in serum were measured by ELISA .The NGF expression was assayed by immunohistochemistry .The expression difference of neurofilament protein mRNA was detected by RT-PCR .Results (1) Electron microscope showed ,medullary cells riched in mitochondria ,Chro-maffin granule concentration decreased obviously ,and membrane could saw clubbing phenomenon of neurite outgrowth clearly in RSV infection group .Meanwhile ,NGF expression was significantly increased in RSV infection group .(2) ELISA results showed that the concentrations of NGF in the RSV group was significantly increased compared with control group and anti-NGF group(P 0 .05) .Compared with control group ,the adrenaline concentration of RSV group and anti-NGF group was significantly decreased(P<0 .01) ,and the adrenaline concentration of RSV group was significantly decreased compared with anti-NGF antibody group(P<0 .05) .(3) NF-LmRNA expression was significantly increased in RSV group .However ,compared with control group ,the NF-LmRNA expression was significantly decreased in anti-NGF group .(4) RT-PCR results show that ,Compared with control group ,adrenal medullary cells NF-LmRNA expression of RSV group and the anti-NGF group was significantly increased .Compared with RSV group ,NF-LmRNA adrenal medulla cells in Anti-NGF group was significantly decreased .Conclusion RSV infection may induce the adrenal medullary cell differentiation to nerve cell by over-expressed NGF ,and result in the decrease of adrenaline in serum to involve in asthma progression .