Mucin Granule Intraluminal Organization

Pérez-Vilar, Juan

doi:10.1165/rcmb.2006-0291tr

Cited by 83 publications

(69 citation statements)

References 64 publications

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“…35,36 It is the only mucin isolated from normal human airway secretions and is therefore proposed to be the key airway secretory mucin. 37 Previous studies indicated that inflammation activated epidermal growth factor receptor and stimulated IL-13 to induce both Clara and ciliated cells to transform to goblet cells, which led to up-regulation of MUC5AC expression and secretion and mucus hypersecretion. 38 In the present study, we also found the promotion of MUC5AC expression in BALF and lung tissue of COPD model rats, which was suppressed by the treatment of hydrogen-rich saline.…”

Section: Liu Et Al Hydrogen-rich Saline Inhibits Ts-induced Copd 1537mentioning

confidence: 99%

Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats

Liu

Geng

Jiang

et al. 2017

Exp Biol Med (Maywood)

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This study was designed to evaluate protective effect of hydrogen-rich saline, a novel antioxidant, on tobacco smoke (TS)-induced chronic obstructive pulmonary disease (COPD) in rats and explore the underlying mechanism. Our results suggest that administration of hydrogen-rich saline improves lung function and alleviates morphological impairments of lung through alleviating inflammation, reducing oxidative stress and lessening mucus hypersecretion in TS-induced COPD rats. AbstractChronic obstructive pulmonary disease induced by tobacco smoke has been regarded as a great health problem worldwide. The purpose of this study is to evaluate the protective effect of hydrogen-rich saline, a novel antioxidant, on chronic obstructive pulmonary disease and explore the underlying mechanism. Sprague-Dawley rats were made chronic obstructive pulmonary disease models via tobacco smoke exposure for 12 weeks and the rats were treated with 10 ml/kg hydrogen-rich saline intraperitoneally during the last 4 weeks. Lung function testing indicated hydrogen-rich saline decreased lung airway resistance and increased lung compliance and the ratio of forced expiratory volume in 0.1 s/forced vital capacity in chronic obstructive pulmonary disease rats. Histological analysis revealed that hydrogen-rich saline alleviated morphological impairments of lung in tobacco smoke-induced chronic obstructive pulmonary disease rats. ELISA assay showed hydrogen-rich saline lowered the levels of pro-inflammatory cytokines (IL-8 and IL-6) and anti-inflammatory cytokine IL-10 in bronchoalveolar lavage fluid and serum of chronic obstructive pulmonary disease rats. The content of malondialdehyde in lung tissue and serum was also determined and the data indicated hydrogen-rich saline suppressed oxidative stress reaction. The protein expressions of mucin MUC5C and aquaporin 5 involved in mucus hypersecretion were analyzed by Western blot and ELISA and the data revealed that hydrogen-rich saline down-regulated MUC5AC level in bronchoalveolar lavage fluid and lung tissue and up-regulated aquaporin 5 level in lung tissue of chronic obstructive pulmonary disease rats. In conclusion, these results suggest that administration of hydrogen-rich saline exhibits significant protective effect on chronic obstructive pulmonary disease through alleviating inflammation, reducing oxidative stress and lessening mucus hypersecretion in tobacco smoke-induced chronic obstructive pulmonary disease rats.

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Section: Liu Et Al Hydrogen-rich Saline Inhibits Ts-induced Copd 1537mentioning

confidence: 99%

Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats

Liu

Geng

Jiang

et al. 2017

Exp Biol Med (Maywood)

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“…Other proteins also exploit pH-dependent interactions between VWF D domains for similar ends. For example, vertebrates have a family gel-forming mucins that make disulfidelinked dimers between C-terminal CK domains in the ER, and disulfide-linked multimers between N-terminal D1D2DЈD3 domains in the Golgi (31). The helical packing of VWF D1D2 and DЈD3 proteins provides a framework to investigate the biogenesis of Weibel-Palade bodies and the assembly of homologous multimeric proteins.…”

Section: Vwf Tubules and The Assembly Of Homologous Multimeric Proteinsmentioning

confidence: 99%

Assembly of Weibel–Palade body-like tubules from N-terminal domains of von Willebrand factor

Huang

Wang²,

Roth³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

149

285

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Lengthwise sections show longitudinal striations, and cross sections reveal closely spaced Ϸ20-nm diameter tubules separated by a less-dense matrix (1). Weibel-Palade bodies are composed almost entirely of von Willebrand factor (VWF) (2, 3), which is a multimeric plasma glycoprotein that can exceed 20 million Da in mass and 4 m in length. Megakaryocytes synthesize large VWF multimers and package them into platelet ␣-granules that are roughly spherical rather than cigar-shaped. Nevertheless, the VWF multimers in ␣-granules are organized into clusters of tubules with dimensions similar to those of VWF tubules in Weibel-Palade bodies (4). VWF is the largest known protein in the blood, and the very largest VWF multimers bind connective tissue and mediate platelet adhesion at sites of vascular injury. Weibel-Palade bodies play a critical role in hemostasis by delivering VWF multimers into the circulation. Defects in VWF multimer structure cause several forms of von Willebrand disease, the most common inherited bleeding disorder worldwide (5).VWF is synthesized as an Ϸ350-kDa precursor with a signal peptide and five kinds of structural domains arranged in the order D1-D2-DЈ-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2-CK ( Fig. 1) (5). In the endoplasmic reticulum (ER), proVWF dimerizes through disulfide bonds between C-terminal CK domains (6-8).The resultant ''tail-to-tail'' proVWF dimers are transported to the Golgi, where the propeptide (domains D1D2) is cleaved by furin and additional ''head-to-head'' disulfide bonds form between D3 domains, yielding multimers that condense into tubules and form Weibel-Palade bodies (6, 9).In fact, the expression of VWF determines the existence and also the cigar-like shape of Weibel-Palade bodies. Without VWF, endothelial cells lack Weibel-Palade bodies (10, 11), and the expression of VWF in other cell types that have a regulated secretory pathway results in the generation of organelles that are indistinguishable from Weibel-Palade bodies (12, 13). This self-organizing behavior depends on a conserved set of Nterminal domains that have the dual function of promoting multimer assembly and directing tubular storage.Multimer assembly (14-16) and tubular packing (12, 17) both depend on the N-terminal D1D2DЈD3 domains and require the acidic pH of the late secretory pathway (13). Furthermore, the tubular morphology of Weibel-Palade bodies is essential for . VWF multimers are held together by intersubunit disulfide bonds between CK domains, which form in the ER, and by intersubunit disulfide bonds between D3 domains, which form in the Golgi. The structures of polypeptides encoded by the plasmids used in these studies are indicated.

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“…These cells can usually be seen histologically by Alcian blue-periodic acid-Schiff (PAS) staining because of the storage of these heavily glycosylated proteins in cytoplasmic secretory granules (8). Normal airway epithelium contains a paucity of surface goblet cells and a moderate number of submucosal glands.…”

Section: Mucins Expressed In the Lungsmentioning

confidence: 99%

Regulation of Airway Mucin Gene Expression

Thai

Loukoianov

Wachi

et al. 2008

Annu. Rev. Physiol.

193

223

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Mucins are important components that exert a variety of functions in cell-cell interaction, epidermal growth factor receptor signaling, and airways protection. In the conducting airways of the lungs, mucins are the major contributor to the viscoelastic property of mucous secretion, which is the major barrier to trapping inhaled microbial organism, particulates, and oxidative pollutants. The homeostasis of mucin production is an important feature in conducting airways for the maintenance of mucociliary function. Aberrant mucin secretion and accumulation in airway lumen are clinical hallmarks associated with various lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, and lung cancer. Among 20 known mucin genes identified, 11 of them have been verified at either the mRNA and/or protein level in airways. The regulation of mucin genes is complicated, as are the mediators and signaling pathways. This review summarizes the current view on the mediators, the signaling pathways, and the transcriptional units that are involved in the regulation of airway mucin gene expression. In addition, we also point out essential features of epigenetic mechanisms for the regulation of these genes.

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Mucin Granule Intraluminal Organization

Cited by 83 publications

References 64 publications

Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats

Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats

Assembly of Weibel–Palade body-like tubules from N-terminal domains of von Willebrand factor

Regulation of Airway Mucin Gene Expression

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