Endothelin-1 Inhibits Mucin Secretion from Ovine Airway Epithelial Goblet Cells

Clancy, Sinead M.; Yeadon, Michael; Parry, John; Yeoman, Mark; Adam, Elizabeth; Schumacher, Udo; Lethem, Michael I.

doi:10.1165/rcmb.2003-0331oc

Cited by 10 publications

(9 citation statements)

References 30 publications

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“…By contrast, ETRB inhibition increased size of goblet cells, which may occur when secretion by goblet cells is inhibited. The inhibition of the secretion in airways epithelium was mediated by the ETRA blocker BQ123 (7). Also, after goblet cell secretes, it resynthesizes mucus and remains Alcian blue positive.…”

Section: Discussionmentioning

confidence: 99%

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Endothelin-3 stimulates survival of goblet cells in organotypic cultures of fetal human colonic epithelium

Kalabis

Li²,

Fukunaga-Kalabis³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Cells within the normal human colonic epithelium undergo a dynamic cycle of growth, differentiation, and death. The organotypic culture system of human fetal colonic epithelial cells seeded on top of collagen gels with embedded colonic fibroblasts allowed prolonged culture of the colonic epithelial cells (Kalabis J, Patterson MJ, Enders GM, Marian B, Iozzo RV, Rogler G, Gimotty PA, Herlyn M. FASEB J 17: 1115-1117, 2003). Herein, we have evaluated the role of endothelin-3 (ET3) and both cognate endothelin receptors (ETRA, ETRB) for human colonic epithelial cell growth and survival. ET3 was produced continuously by the fibroblasts as a result of adenovirus-mediated gene transfer. The presence and function of the endothelin receptors (ETRs) in epithelial cells was evaluated by [(3)H]thymidine incorporation using primary epithelial cells in monoculture and by immunohistochemistry on human fetal and adult paraffin-embedded tissues. In organotypic culture, ET3 increased the number of goblet cells but not of enteroendocrine cells. The increase in goblet cells was caused by prolonged cell survival and differentiation. The inhibition of both ETRA and ETRB significantly decreased the number of goblet cells and proliferation in epithelial cells, whereas the number of enteroendocrine cells remained unchanged. ET3 induced activation of IkappaB and MAPK in the epithelial cells, suggesting that these signaling pathways mediate its proproliferation and prosurvival activities. Our results demonstrate that ET3 is involved in regulating human colonic epithelial cell proliferation and survival, particularly for goblet cells, and may be an important component of colonic homeostasis.

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Section: Discussionmentioning

confidence: 99%

“…Recently, ET1 was shown to block secretion of mucin from bovine airways epithelial cells (7). By contrast, ETRB inhibition increased size of goblet cells, which may occur when secretion by goblet cells is inhibited.…”

Section: Discussionmentioning

confidence: 99%

Endothelin-3 stimulates survival of goblet cells in organotypic cultures of fetal human colonic epithelium

Kalabis

Li²,

Fukunaga-Kalabis³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Because lectins are glycan specific, they are not mucin specific and their rigorous use therefore requires validation (e.g., 16–18). Our laboratory uses WGA, specific for GlcNAc β1–4GlcNAc β1–4GlcNAc and Neu5Ac (sialic acid), to detect mucins from HBE cell cultures and mouse tracheas.…”

Section: Methodsmentioning

confidence: 99%

Studying Mucin Secretion from Human Bronchial Epithelial Cell Primary Cultures

Abdullah

Wolber

Kesımer

et al. 2011

Methods in Molecular Biology

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Mucin secretion is regulated by extracellular signaling molecules emanating from local, neuronal, or endocrine sources. Quantifying the rate of this secretion is important to understanding how the exocytic process is regulated, and also how goblet/mucous cells synthesize and release mucins under control and pathological conditions. Consequently, measuring mucins in a quantitatively accurate manner is the key to many experiments addressing these issues. This paper describes procedures used to determine agonist-induced mucin secretion from goblet cells in human bronchial epithelial (HBE) cell cultures. It begins with primary epithelial cell culture, offers methods for purifying MUC5AC and MUC5B mucins for standards, and describes five different microtiter plate binding assays which use various probes for mucins. A polymeric mucin-specific antibody is used in standard and sandwich ELISA formats for two assays while the others target the extensive glycosylated domains of mucins with lectin, periodate oxidation, and antibody-based probes. Comparing the data derived from the different assays applied to the same set of samples of HBE cell cultures indicates a qualitative agreement between baseline and agonist stimulated mucin release; however, the polymeric mucin-specific assays yield substantially lower values than the assays using nonspecific molecular reporters. These results indicate that the more non-specific assays are suitable to assess overall secretory responses by goblet cells, but are likely unsuited for specific measurements of polymeric mucins, per se.

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“…It is well established that extracellular ATP is a potent stimulus for regulated mucus secretion via purinergic receptors [24] , [25] , [26] . Moreover, it is possible to enhance mucin secretion in certain models of the airway epithelium using ATP or its non-hydrolysable analogue, AMP-PNP [27] , [28] , [29] . Therefore, the effect of mucus on drug absorption can be studied by comparing drug absorption in the presence of normal mucus levels and mucus levels increased by ATP (or AMP-PNP).…”

Section: Introductionmentioning

confidence: 99%