MUC16 is produced in tracheal surface epithelium and submucosal glands and is present in secretions from normal human airway and cultured bronchial epithelial cells

Davies, Julia R.; Kirkham, Sara; Svitacheva, Naila; Thornton, David J.; Carlstedt, Ingemar

doi:10.1016/j.biocel.2007.05.013

Cited by 77 publications

(76 citation statements)

References 34 publications

(34 reference statements)

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“…reported (17). These findings indicate that SPDEF regulates a number of genes involved in mucin synthesis, its glycosylation, and packaging.…”

Section: Discussionmentioning

confidence: 82%

“…SPDEF induced expression of a number of genes involved in the regulation of many aspects of mucus production, including protein glycosylation and mucin secretion, as well as genes that are highly represented in experiments in which mice were exposed to pulmonary allergens or IL-13. For example, mucin 16 (Muc16) (17), anterior gradient 2 (Agr2) (Xenopus laevis) (18,19), chloride channel calcium activated 1 (Clca1) (20), prostaglandin E receptor 3 (subtype EP3) prostaglandin E receptor 4 (subtype EP4) (Ptger3/4) (21,22), glucosaminyl (N-acetyl) transferase 3, mucin type (Gcnt3) (23), Foxa3 (13), serine (or cysteine) peptidase inhibitor, clade B (ovalbumin) member 11 (Serpinb11) (24), lumican, and versican (25) were markedly induced by SPDEF. Although Muc5ac mRNA was increased 2-fold by SPDEF, it was prefiltered out because of the low hybridization signals (close to background signal).…”

Section: Cellular Origins Of Goblet Cells Induced By Allergen Exposurementioning

confidence: 99%

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SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production

Chen¹,

Korfhagen²,

Xu³

et al. 2009

J. Clin. Invest.

295

466

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Various acute and chronic inflammatory stimuli increase the number and activity of pulmonary mucus-producing goblet cells, and goblet cell hyperplasia and excess mucus production are central to the pathogenesis of chronic pulmonary diseases. However, little is known about the transcriptional programs that regulate goblet cell differentiation. Here, we show that SAM-pointed domain-containing Ets-like factor (SPDEF) controls a transcriptional program critical for pulmonary goblet cell differentiation in mice. Initial cell-lineage-tracing analysis identified nonciliated secretory epithelial cells, known as Clara cells, as the progenitors of goblet cells induced by pulmonary allergen exposure in vivo. Furthermore, in vivo expression of SPDEF in Clara cells caused rapid and reversible goblet cell differentiation in the absence of cell proliferation. This was associated with enhanced expression of genes regulating goblet cell differentiation and protein glycosylation, including forkhead box A3 (Foxa3), anterior gradient 2 (Agr2), and glucosaminyl (N-acetyl) transferase 3, mucin type (Gcnt3). Consistent with these findings, levels of SPDEF and FOXA3 were increased in mouse goblet cells after sensitization with pulmonary allergen, and the proteins were colocalized in goblet cells lining the airways of patients with chronic lung diseases. Deletion of the mouse Spdef gene resulted in the absence of goblet cells in tracheal/laryngeal submucosal glands and in the conducting airway epithelium after pulmonary allergen exposure in vivo. These data show that SPDEF plays a critical role in regulating a transcriptional network mediating the goblet cell differentiation and mucus hyperproduction associated with chronic pulmonary disorders.

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“…reported (17). These findings indicate that SPDEF regulates a number of genes involved in mucin synthesis, its glycosylation, and packaging.…”

Section: Discussionmentioning

confidence: 82%

Section: Cellular Origins Of Goblet Cells Induced By Allergen Exposurementioning

confidence: 99%

SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production

Chen¹,

Korfhagen²,

Xu³

et al. 2009

J. Clin. Invest.

295

466

View full text Add to dashboard Cite

show abstract

“…Serine and threonine are sites of O-linked glycosylation for the peptide backbone [28,29]. From the 22 known human mucin genes 16 mucins genes are expressed in the lung, of which Muc1, Muc4, Muc5AC, Muc5B, and Muc16 reveal the highest expression profiles [30][31][32][33][34]. There are two different types of mucins, the membrane-tethered mucins like Muc1, Muc4, and MucC16, which contribute to the periciliary layer, and the secreted gel-forming mucins like Muc5AC and Muc5B, which form the upper gel-layer and determine the mucus viscosity [28,[35][36][37].…”

Section: Journal Of Clinical and Cellular Immunologymentioning

confidence: 99%

Small Airways in Asthma: Distal is Different

Vock¹,

Lunding²,

Fehrenbach³

et al. 2017

J Clin Cell Immunol

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“…Sympathetic nerves release the catecholamine noradrenaline (NA). Catecholamines bind to adreno-MUC5AC, MUC5B, MUC7, MUC8, MUC11, MUC13, MUC15, MUC16, MUC18, MUC19, MUC20, MUC21, and MUC22) mucin genes are expressed (19,31,35,56,63,68). The predicted amino acid sequences of the cloned mucin genes revealed that there are 2 types of mucin groups in humans: secreted and membrane-tethered mucins.…”

Section: +mentioning

confidence: 99%

α1-Adrenoceptors relate Ca2+ modulation and protein secretions in rat lacrimal gland

et al. 2015

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Noradrenaline (NA) is a catecholamine with multiple roles including as a hormone and a neurotransmitter. Cellular secretory activities are enhanced by adrenergic stimuli as well as by cholinergic stimuli. The present study aimed to determine which adrenoceptors play a role in controlling intracellular calcium ion ([Ca 2+ ] i ) level in acinar cells of rat lacrimal glands. Expression of mRNA for adrenoceptor subtypes in the acinar cells was assessed using RT-PCR. ] i increase. The peroxidase activity was quantified as a measure of mucin secretion. Ca 2+ -dependent exocytotic secretion of peroxidase was detected in rat lacrimal glands. The RT-PCR results showed that MUC1, MUC4, MUC5AC, MUC5B, and MUC16 were expressed in acinar cells. These findings indicated that NA activates α1-adrenoceptors, which were found to be the main receptors in Ca 2+ -related cell homeostasis and protein (including mucin) secretion in lacrimal glands.The lacrimal gland is the main contributor to the aqueous component of the preocular tear film, which contains water, electrolytes, proteins, peroxidase, mucins, and lactoferrin. The lacrimal gland is composed of several cell types, including myoepithelial cells, ductal cells, goblet cells, and acinar cells, which are the major cell type constituting 80% of the gland. Acinar cells are highly polarized and joined by tight junctions at the luminal membrane, creating distinct basolateral and apical membranes (12). Goblet cells are a source of mucus in tears and secrete different types of mucins onto the ocular surface, especially in the conjunctiva. Although the number of goblet cells increases in the nasolacrimal duct, as the diameter of the nasolacrimal duct lumen is narrower than that of the lacrimal sac. Regulation of lacrimal gland fluid secretions is under neural control; activation of the sensory nerves in the cornea and conjunctiva initiates an afferent pathway leading to the central nervous system, which subsequently activates an efferent pathway that stimulates parasympathetic and sympathetic nerves, and ultimately, the lacrimal gland (32). The appropriate amount and composition of lacrimal gland fluid are crucial for a healthy, intact ocular surface (14). Sympathetic nerves release the catecholamine noradrenaline (NA). Catecholamines bind to adreno-

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MUC16 is produced in tracheal surface epithelium and submucosal glands and is present in secretions from normal human airway and cultured bronchial epithelial cells

Cited by 77 publications

References 34 publications

SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production

SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production

Small Airways in Asthma: Distal is Different

<b>α1-Adrenoceptors relate Ca</b><sup><b>2+</b></sup><b> modulation and protein secretions in rat lacrimal </b><b>gland </b>

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