Emphysema,myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution,especially fine particulate matter(PM_(2.5)),leading to chronic obstructive pulmonary disease(...Emphysema,myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution,especially fine particulate matter(PM_(2.5)),leading to chronic obstructive pulmonary disease(COPD).Specifically,bronchial epithelium-fibroblast communication participates in airway remodeling,which results in COPD.An increasing number of studies are now being conducted on the role of exosome-mediated cell-cell communication in disease pathogenesis.Here,we investigated whether exosomes generated from bronchial epithelial cells could deliver information to normal stromal fibroblasts and provoke cellular responses,resulting in airway obstruction in COPD.We studied the mechanism of exosome-mediated intercellular communication between human bronchial epithelial(HBE) cells and primary lung fibroblasts(pLFs).We found that PM_(2.5)-induced HBE-derived exosomes promoted myofibroblast differentiation in pLFs.Then,the exosomal lncRNA expression profiles derived from PM_(2.5)-treated HBE cells and nontreated HBE cells were investigated using an Agilent Human LncRNA Array.Combining coculture assays and direct exosome treatment,we found that HBE cell-derived exosomal HOTAIRM1 facilitated the myofibroblast differentiation of pLFs.Surprisingly,we discovered that exosomal HOTAIRM1 enhanced p LF proliferation to secrete excessive collagen secretion,leading to airway obstruction by stimulating the TGF-β/SMAD3 signaling pathway.Significantly,PM_(2.5)reduced FEV1/FVC and FEV1 and increased the level of serum exosomal HOTAIRM1 in healthy people;moreover,serum exosomal HOTAIRM1 was associated with PM_(2.5)-related reductions in FEV1/FVC and FVC.These findings show that PM_(2.5)triggers alterations in exosome components and clarify that one of the paracrine mediators of myofibroblast differentiation is bronchial epithelial cell-derived HOTAIRM1,which has the potential to be an effective prevention and therapeutic target for PM_(2.5)-induced COPD.展开更多
Previous studies have shown that exposure to black carbon(BC,a tracer of traffic-related air pollution)and psychosocial stress are both associated with adverse cardiac effects,but whether psychosocial stress could mod...Previous studies have shown that exposure to black carbon(BC,a tracer of traffic-related air pollution)and psychosocial stress are both associated with adverse cardiac effects,but whether psychosocial stress could modify the cardiac effects of BC is unclear.To investigate the potential modifying effect of psychosocial stress on the associations between acute exposure to BC and typical cardiac health variables,real-time personal 24 h measurements were conducted in a repeated-measure study among adults with elevated blood pressure(high-risk group)and a panel study among normal adults(low-risk group)in China.Measured cardiac health variables included ST-segment depression events,heart rate,and heart rate variability(HRV)variables.Perceived Stress Scale,State Anxiety Inventory and Self-rating Depression Scale were used to assess the recent psychosocial stress status of the participants,and a composite stress index was established based on these scales.Generalized linear mixed-effects model was used to analyze the associations between BC exposure and cardiac health variables and potential effect modification by psychosocial stress.A total of 9724 h measurements among 97 participants in the repeated-measure study and 20224 h measurements among 87 participants in the panel study were included in the final analysis.Acute BC exposure was significantly associated with increased ST-segment depression events and heart rate and decreases in HRV in both studies.The marginal effects of acute BC exposure on most cardiac health variables generally tended to be amplified under higher vs low levels of psychosocial stress in both studies,with the composite stress index apparently modifying the associations of BC exposure with most ST-segment depression events and HRV variables.These findings suggest that psychosocial stress may increase the participants’cardiac susceptibility to BC exposure,which could be helpful for the identification of susceptible individuals in the context of traffic-related air pollution.展开更多
基金supported by the National Natural Science Foundation of China (21777100, 81803267)。
文摘Emphysema,myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution,especially fine particulate matter(PM_(2.5)),leading to chronic obstructive pulmonary disease(COPD).Specifically,bronchial epithelium-fibroblast communication participates in airway remodeling,which results in COPD.An increasing number of studies are now being conducted on the role of exosome-mediated cell-cell communication in disease pathogenesis.Here,we investigated whether exosomes generated from bronchial epithelial cells could deliver information to normal stromal fibroblasts and provoke cellular responses,resulting in airway obstruction in COPD.We studied the mechanism of exosome-mediated intercellular communication between human bronchial epithelial(HBE) cells and primary lung fibroblasts(pLFs).We found that PM_(2.5)-induced HBE-derived exosomes promoted myofibroblast differentiation in pLFs.Then,the exosomal lncRNA expression profiles derived from PM_(2.5)-treated HBE cells and nontreated HBE cells were investigated using an Agilent Human LncRNA Array.Combining coculture assays and direct exosome treatment,we found that HBE cell-derived exosomal HOTAIRM1 facilitated the myofibroblast differentiation of pLFs.Surprisingly,we discovered that exosomal HOTAIRM1 enhanced p LF proliferation to secrete excessive collagen secretion,leading to airway obstruction by stimulating the TGF-β/SMAD3 signaling pathway.Significantly,PM_(2.5)reduced FEV1/FVC and FEV1 and increased the level of serum exosomal HOTAIRM1 in healthy people;moreover,serum exosomal HOTAIRM1 was associated with PM_(2.5)-related reductions in FEV1/FVC and FVC.These findings show that PM_(2.5)triggers alterations in exosome components and clarify that one of the paracrine mediators of myofibroblast differentiation is bronchial epithelial cell-derived HOTAIRM1,which has the potential to be an effective prevention and therapeutic target for PM_(2.5)-induced COPD.
基金supported by the National Natural Science Foundation of China (82073509)the National Key Research and Development Program of China (2017YFC0211600,2017YFC0211601).
文摘Previous studies have shown that exposure to black carbon(BC,a tracer of traffic-related air pollution)and psychosocial stress are both associated with adverse cardiac effects,but whether psychosocial stress could modify the cardiac effects of BC is unclear.To investigate the potential modifying effect of psychosocial stress on the associations between acute exposure to BC and typical cardiac health variables,real-time personal 24 h measurements were conducted in a repeated-measure study among adults with elevated blood pressure(high-risk group)and a panel study among normal adults(low-risk group)in China.Measured cardiac health variables included ST-segment depression events,heart rate,and heart rate variability(HRV)variables.Perceived Stress Scale,State Anxiety Inventory and Self-rating Depression Scale were used to assess the recent psychosocial stress status of the participants,and a composite stress index was established based on these scales.Generalized linear mixed-effects model was used to analyze the associations between BC exposure and cardiac health variables and potential effect modification by psychosocial stress.A total of 9724 h measurements among 97 participants in the repeated-measure study and 20224 h measurements among 87 participants in the panel study were included in the final analysis.Acute BC exposure was significantly associated with increased ST-segment depression events and heart rate and decreases in HRV in both studies.The marginal effects of acute BC exposure on most cardiac health variables generally tended to be amplified under higher vs low levels of psychosocial stress in both studies,with the composite stress index apparently modifying the associations of BC exposure with most ST-segment depression events and HRV variables.These findings suggest that psychosocial stress may increase the participants’cardiac susceptibility to BC exposure,which could be helpful for the identification of susceptible individuals in the context of traffic-related air pollution.
