scholarly journals Guifu Dihuang Pills Ameliorated Mucus Hypersecretion by Suppressing Muc5ac Expression and Inactivating the ERK-SP1 Pathway in Lipopolysaccharide/Cigarette Smoke-Induced Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Huanhuan Zhang ◽  
Wenying Yu ◽  
Liting Ji ◽  
Yusen Zhong ◽  
Yiyou Lin ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Cigarette Smoke ◽  
Goblet Cell ◽  
Periodic Acid ◽  
Lung Damage ◽  
Pathological Changes ◽  
Cell Hyperplasia ◽  
Mucus Hypersecretion ◽  
Goblet Cell Hyperplasia ◽  
Expression Levels

Mucus hypersecretion is a hallmark of chronic obstructive pulmonary disease (COPD) and is associated with increasing sputum production and declining pulmonary function. Therefore, reducing mucus secretion can be a new therapeutic opportunity for preventing COPD. The Guifu Dihuang pill (GFDHP) is a classical Chinese medicine and has been used as an immunoregulator for treatment of kidney yang deficiency syndrome, including hypothyroidism, adrenocortical hypofunction, chronic bronchitis, and COPD, for more than 2000 years. However, the protective effects and mechanisms of GFDHP against mucus hypersecretion in COPD remain obscure. The aim of the present study was to explore the inhibitory effects of GFDHP on lipopolysaccharide/cigarette smoke- (LPS/CS-) induced Mucin5ac (Muc5ac) overproduction and airway goblet cell hyperplasia in mice. The mice were randomly assigned into 6 groups: control, model, GFDHP-L, GFDHP-M, GFDHP-H, and dexamethasone. The mice were given LPS twice through intranasal inhalation and then exposed to CS daily for 6 weeks. Three doses of GFDHP were orally administered daily during the last 3 weeks of the experiment. Pulmonary function was examined with an EMKA pulmonary system, and pulmonary hyperpermeability and lung damage were evaluated with an in vivo imaging system. Inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were detected with a cell count analyzer and though ELISA analysis, respectively. Lung pathological changes and airway goblet cell hyperplasia were analyzed with hematoxylin and eosin and Alcian blue periodic acid Schiff staining. The protein expression levels of Muc5ac and extracellular signal-regulated kinase (ERK)-specificity protein1 (SP1) signaling pathway were measured with Western blot and immunohistochemistry. The results demonstrated that GFDHP improved pulmonary function and suppressed mouse pulmonary hyperpermeability and edema. GFDHP suppressed inflammatory cell infiltration and cytokine release in BALF, thereby elevating pulmonary function. It ameliorated lung pathological changes and airway goblet cell hyperplasia, and suppressed expression levels of Muc5ac mRNA and protein and phospho-ERK and SP1 levels in the lung tissues of the COPD mice. In conclusion, GFDHP inhibited mucus hypersecretion induced by LPS/CS by suppressing the activation of the ERK-SP1 pathway.

scholarly journals WNT/RYK signaling restricts goblet cell differentiation during lung development and repair

2019 ◽  
Vol 116 (51) ◽  
pp. 25697-25706 ◽  
Author(s):  
Hyun-Taek Kim ◽  
Wenguang Yin ◽  
Yuko Nakamichi ◽  
Paolo Panza ◽  
Beate Grohmann ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cells ◽  
Goblet Cell ◽  
Lung Development ◽  
Alveolar Epithelial Cells ◽  
Airway Epithelial ◽  
Cell Hyperplasia ◽  
Mucus Hypersecretion ◽  
Goblet Cell Hyperplasia ◽  
Goblet Cell Differentiation

Goblet cell metaplasia and mucus hypersecretion are observed in many pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the regulation of goblet cell differentiation remains unclear. Here, we identify a regulator of this process in anN-ethyl-N-nitrosourea (ENU) screen for modulators of postnatal lung development;Rykmutant mice exhibit lung inflammation, goblet cell hyperplasia, and mucus hypersecretion. RYK functions as a WNT coreceptor, and, in the developing lung, we observed high RYK expression in airway epithelial cells and moderate expression in mesenchymal cells as well as in alveolar epithelial cells. From transcriptomic analyses and follow-up studies, we found decreased WNT/β-catenin signaling activity in the mutant lung epithelium. Epithelial-specificRykdeletion causes goblet cell hyperplasia and mucus hypersecretion but not inflammation, while club cell-specificRykdeletion in adult stages leads to goblet cell hyperplasia and mucus hypersecretion during regeneration. We also found that the airway epithelium of COPD patients often displays goblet cell metaplastic foci, as well as reduced RYK expression. Altogether, our findings reveal that RYK plays important roles in maintaining the balance between airway epithelial cell populations during development and repair, and that defects in RYK expression or function may contribute to the pathogenesis of human lung diseases.

scholarly journals Current smoking with or without chronic bronchitis is independently associated with goblet cell hyperplasia in healthy smokers and COPD subjects

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Victor Kim ◽  
Stephanie Jeong ◽  
Huaqing Zhao ◽  
Mehmet Kesimer ◽  
Richard C. Boucher ◽  
...  
Keyword(s):  
Chronic Bronchitis ◽  
Goblet Cell ◽  
Clinical Symptoms ◽  
Periodic Acid ◽  
Airflow Obstruction ◽  
Active Smoking ◽  
Cell Hyperplasia ◽  
Current Smoking ◽  
Goblet Cell Hyperplasia ◽  
Former Smokers

AbstractCOPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects]. Endobronchial mucosal biopsies were stained with Periodic Acid Schiff-Alcian Blue, and GCD was measured as number of goblet cells/mm basement membrane. GCD was divided into tertiles based on log10 transformed values. Log10GCD was greater in current smokers compared to former smokers. Those with classically defined CB or SGRQ defined CB had a greater log10 GCD compared to those without CB. Current smoking was independently associated with tertile 3 (high log10GCD) whereas CB was not in multivariable regression when adjusting for lung function and demographics. These results suggest that GCH is induced by active smoke exposure and does not necessarily correlate with the clinical symptoms of CB.

scholarly journals Current Smoking With or Without Chronic Bronchitis is Independently Associated With Goblet Cell Hyperplasia in Healthy Smokers and COPD Subjects: an Analysis of the SPIROMICS Cohort

2020 ◽  
Author(s):  
Victor Kim ◽  
Stephanie Jeong ◽  
Huaqing Zhao ◽  
Jennifer Kraft ◽  
Mehmet Kesimer ◽  
...  
Keyword(s):  
Chronic Bronchitis ◽  
Goblet Cell ◽  
Clinical Symptoms ◽  
Periodic Acid ◽  
Airflow Obstruction ◽  
Active Smoking ◽  
Cell Hyperplasia ◽  
Current Smoking ◽  
Goblet Cell Hyperplasia ◽  
Former Smokers

Abstract Background: COPD, chronic bronchitis (CB) and active smoking have all been associated with large airway goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Methods: Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects] in which endobronchial mucosal biopsies were obtained during the SPIROMICS bronchoscopy substudy. Biopsies were stained with Periodic Acid Schiff-Alcian Blue, and GCD was measured as number of goblet cells/mm basement membrane by two independent observers in a blinded fashion. GCD was divided into tertiles (1=low, 2=medium, 3=high) based on log10 transformed values. Multivariable logistic and linear regressions were performed with CB and current smoking as the independent variables of interest and demographics and FEV1% predicted smoking as covariates.Results: Log10 GCD was greater in current smokers compared to former smokers (1.16±0.28 [n=31] vs. 0.85±0.42 [n=40], p=0.001). Those with classically defined CB had a greater log10 GCD compared to those without CB (1.21±0.31 [n=13] vs. 0.94±0.39 [n=58], p=0.024). Similarly, those with CB by the SGRQ definition had a greater log10 GCD compared to those without CB (1.13±0.39 [n=25] vs. 0.91±0.39 [n=43], p=0.028). Tertiles 2 and 3 had a greater percent of current smokers compared to tertile 1 (16.7, 50.0 and 63.6% in tertiles 1, 2 and 3, respectively, p=0.004). Current smoking was independently associated with tertile 3 (high GCD) (OR 4.15, 95% CI 1.17, 14.71) whereas CB was not in multivariable logistic regression. Similar results were found with multivariable linear regression for log10 GCD.Conclusions: GCD is higher in current smokers with and without airflow obstruction and in CB. However, current smoking, but not CB, is independently associated with GCD. These results suggest that GCH is induced by active smoke exposure and does not necessarily correlate with the clinical symptoms of CB.

scholarly journals PENGARUH PERUBAHAN HIPERPLASIA SEL GOBLET SELAMA 28 HARI PAPARAN ASAP ROKOK DENGAN PEMBERIAN ANTIOKSIDAN SUPEROXIDE DISMUTASE

2017 ◽  
Vol 11 (1) ◽  
pp. 60
Author(s):  
Rivan Virlando Suryadinata ◽  
Bambang Wirjatmadi ◽  
Merryana Adriani
Keyword(s):  
Superoxide Dismutase ◽  
Goblet Cell ◽  
Longitudinal Section ◽  
Positive Control ◽  
Negative Control ◽  
Cell Hyperplasia ◽  
Mucus Hypersecretion ◽  
Goblet Cell Hyperplasia ◽  
Treatment Groups ◽  
Different Doses

The number of Indonesian smokers in 2013 has reached 36.3% and continues to increase each year. This will directly affect the increase in passive smokers in Indonesia. Harmful free radicals from cigarette smoke inhaled can lead to irritation of the bronchial airways. Irritation of the airways characterized by mucus hypersecretion induced goblet cell hyperplasia of the bronchi. Giving antioxidants superoxide dismutase melon extract with a combination of gliadin (SOD-gliadin) reduces radical that goblet cell hyperplasia in the bronchial airways can be reduced. This study aims to determine the effectiveness of the SOD-gliadin to the decrease of goblet cell hyperplasia of the bronchi. Giving SOD-gliadin carried out for 28 days with exposure to smoke two cigarettes per day using 5 groups: negative control, positive control and 3 treatment groups with different doses (2,25 IU; 4,5 IU; 9 IU). Observation of goblet cell hyperplasia performed on histological preparations with a longitudinal section with four visual field. With the effects of the antioxidant superoxide dismutase melon extract on percentage of goblet cell hyperplasia (ANOVA, p = 0396). It can be concluded supplementation with SOD-gliadin not influence the percentage of goblet cell hyperplasia.Keywords: goblet cell, superoxide dismutase, antioxidants, cigarette, free radical

scholarly journals The development of an in vitro 3D model of goblet cell hyperplasia using MUC5AC expression and repeated whole aerosol exposures

2021 ◽  
Author(s):  
Linsey E. Haswell ◽  
David Smart ◽  
Tomasz Jaunky ◽  
Andrew Baxter ◽  
Simone Santopietro ◽  
...  
Keyword(s):  
Goblet Cell ◽  
3D Model ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia
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