Background Airway mucus hypersecretion is an important pathophysiological feature of chronic obstructive pulmonary disease, which is closely associated with cigarette smoking. However, the signal transduction pathway ...Background Airway mucus hypersecretion is an important pathophysiological feature of chronic obstructive pulmonary disease, which is closely associated with cigarette smoking. However, the signal transduction pathway from the cell surface to the nucleus through which cigarette smoke causes upregulation of mucin gene expression is not well known. This study was designed to investigate the role of extracellular signal-regulated Kinase 1/2 （ERK 1/2） in airway mucus hypersecretion induced by cigarette smoke in rats. Methods A rat model of airway mucus hypersecretion was induced by exposure to cigarette smoke for 4 weeks. Rats exposed to inhalation of cigarette smoke or normal saline were given an intraperitoneal injection of U0126, a specific MEK1 kinase inhibitor, at doses of 0.25 mg/kg, 0.5 mg/kg and 1 mg/kg for 14 days. Expression of MUC5AC mRNA and protein, ERK 1/2 and phosphorylated-ERK 1/2 （p-ERK 1/2） were detected by RT-PCR, immunohistochemistry and Western blotting. Results Cigarette smoke significantly increased airway goblet cells metaplasia, induced the overexpression of MUC5AC mRNA and protein in bronchial epithelia, and increased the ratio of p-ERK 1/2 and ERK 1/2. U0126 significantly attentuated the expression of MUC5AC mRNA and protein induced by cigarette smoke （P 〈0.05）. Moreover, there was a significant positive correlation between the ratio of p-ERK1/2 to ERK1/2 and the expression of MUC5AC mRNA and protein （P 〈0.05）. Conclusions Inhibition of ERK 1/2 by U0126 decreased the ratio of p-ERK 1/2 to ERK 1/2 and expression of MUC5AC mRNA and protein. ERK 1/2 may play an essential role in cigarette smoke-induced mucus hypersecretion in vivo.展开更多
Background Monilethrix is an autosomal dominant hair disorder characterized clinically by alopecia and follicular papules.In this study,we collected a Han monilethrix family to detect the mutations in patients and inv...Background Monilethrix is an autosomal dominant hair disorder characterized clinically by alopecia and follicular papules.In this study,we collected a Han monilethrix family to detect the mutations in patients and investigated the correlation between the genotype and phenotype of monilethrix.Methods In this study,we identified a Chinese family with monilethrix through light microscopic and scanning electron microscopic （SEM） examination.Genomic DNA from peripheral blood samples was prepared.DNA samples from controls and monilethrix patients were subject to polymerase chain reaction （PCR） amplification.Two pairs of primers were used to amplify the seventh exon of KRT86.Mutation screening of the PCR products was detected using direct sequencing.Results Light microscopic examination showed a regular alternate enlargement and narrow area.SEM examination showed that part of the cuticle of the nodules shed and disappeared gradually in the narrow area with granular protrusions on the surface similar to the erosion-like structure.Parallel longitudinal ridge and groovepattern appeared,and the ridges varied in width,like dead wood.A heterozygous transversion mutation c.1204G＞A（p.E402K） in the seventh exon of KRT86 was identified in both patients.Conclusions The mutation of extron 7 of KRT86 identified plays a major role in the pathogenesis of this pedigree with monilethrix,and is a mutation hot spot of KRT86.Further research is needed to explore the relationship between the phenotype and the mutation of the type Ⅱ hair keratin gene KRT86 of monilethrix.展开更多
基金This study was supported by a grant from China Postdoctoral Science Foundation （No. 37508）.
文摘Background Airway mucus hypersecretion is an important pathophysiological feature of chronic obstructive pulmonary disease, which is closely associated with cigarette smoking. However, the signal transduction pathway from the cell surface to the nucleus through which cigarette smoke causes upregulation of mucin gene expression is not well known. This study was designed to investigate the role of extracellular signal-regulated Kinase 1/2 （ERK 1/2） in airway mucus hypersecretion induced by cigarette smoke in rats. Methods A rat model of airway mucus hypersecretion was induced by exposure to cigarette smoke for 4 weeks. Rats exposed to inhalation of cigarette smoke or normal saline were given an intraperitoneal injection of U0126, a specific MEK1 kinase inhibitor, at doses of 0.25 mg/kg, 0.5 mg/kg and 1 mg/kg for 14 days. Expression of MUC5AC mRNA and protein, ERK 1/2 and phosphorylated-ERK 1/2 （p-ERK 1/2） were detected by RT-PCR, immunohistochemistry and Western blotting. Results Cigarette smoke significantly increased airway goblet cells metaplasia, induced the overexpression of MUC5AC mRNA and protein in bronchial epithelia, and increased the ratio of p-ERK 1/2 and ERK 1/2. U0126 significantly attentuated the expression of MUC5AC mRNA and protein induced by cigarette smoke （P 〈0.05）. Moreover, there was a significant positive correlation between the ratio of p-ERK1/2 to ERK1/2 and the expression of MUC5AC mRNA and protein （P 〈0.05）. Conclusions Inhibition of ERK 1/2 by U0126 decreased the ratio of p-ERK 1/2 to ERK 1/2 and expression of MUC5AC mRNA and protein. ERK 1/2 may play an essential role in cigarette smoke-induced mucus hypersecretion in vivo.
文摘Background Monilethrix is an autosomal dominant hair disorder characterized clinically by alopecia and follicular papules.In this study,we collected a Han monilethrix family to detect the mutations in patients and investigated the correlation between the genotype and phenotype of monilethrix.Methods In this study,we identified a Chinese family with monilethrix through light microscopic and scanning electron microscopic （SEM） examination.Genomic DNA from peripheral blood samples was prepared.DNA samples from controls and monilethrix patients were subject to polymerase chain reaction （PCR） amplification.Two pairs of primers were used to amplify the seventh exon of KRT86.Mutation screening of the PCR products was detected using direct sequencing.Results Light microscopic examination showed a regular alternate enlargement and narrow area.SEM examination showed that part of the cuticle of the nodules shed and disappeared gradually in the narrow area with granular protrusions on the surface similar to the erosion-like structure.Parallel longitudinal ridge and groovepattern appeared,and the ridges varied in width,like dead wood.A heterozygous transversion mutation c.1204G＞A（p.E402K） in the seventh exon of KRT86 was identified in both patients.Conclusions The mutation of extron 7 of KRT86 identified plays a major role in the pathogenesis of this pedigree with monilethrix,and is a mutation hot spot of KRT86.Further research is needed to explore the relationship between the phenotype and the mutation of the type Ⅱ hair keratin gene KRT86 of monilethrix.
