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What Is The Function Of Goblet Cells

What Is The Function Of Goblet Cells

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Goblet Cell Lrrc26 Regulates Bk Channel Activation And Protects Against Colitis In Mice

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Janice J. Kim Janice J. Kim Scilit Preprints.org Google Scholar 1, 2 and Waliul I. Khan Waliul I. Khan Scilit Preprints.org Google Scholar 1, 2, *

Received: 2013 January 9 / Revised: 2013 January 27 / Adopted: 2013 January 28 / Published in 2013 February 4

Studies Of Different Goblet Cells And Proteins Involved In Mucus Protection Of The Intestinal Epithelium

Goblet cells are found throughout the gastrointestinal (GI) tract and are responsible for producing and maintaining a protective mucus blanket by synthesizing and secreting high molecular weight glycoproteins known as mucins. The concept of a mucus layer acting as a dynamic protective barrier is suggested by studies showing changes in mucins in inflammatory diseases of the gastrointestinal tract, altered goblet cell responses in germ-free animals, and increased mucus secretion seen in response to infections. The mucin-rich mucus layer lining the GI epithelium is the front line of innate host defense. Mucins are likely to be the first molecules that invading pathogens interact with at the cell surface, and may therefore limit binding to other glycoproteins and neutralize the pathogen. This review will focus on what is known about the goblet cell response to various GI infections and the regulatory networks that mediate goblet cell function and mucin production in response to intestinal injury. Furthermore, we describe the current knowledge on the role of mucins in the innate defense of the gut. The purpose of this review is to provide readers with an up-to-date information on goblet cell biology and the current understanding of the role of mucins in host defense in intestinal infection.

The luminal side of the gastrointestinal (GI) mucosal layer is covered by a mucus blanket that protects the mucosa from desiccation and mechanical damage and forms a physical barrier between the underlying epithelium and the luminal contents containing pathogenic bacteria and viruses. , and parasites [1, 2]. Nevertheless, mucus is permeable to components of low molecular weight and this property is important for the absorption of nutrients in the intestine. Mucus contains high molecular weight glycoproteins known as mucins as major components, which are secreted by goblet cells [3, 4]. Goblet cells are present throughout the gastrointestinal tract and are the main source of intestinal mucins [5]. The concept of a mucus layer acting as a dynamic protective barrier was suggested by studies showing changes in mucins under inflammatory intestinal conditions, altered goblet cell responses in germ-free animals, and increased mucus secretion observed in response to infections. [6, 7].

The GI tract is constantly exposed to a wide range of foodborne and waterborne pathogens, as well as endogenous microbiota adapted for symbiotic life in the gut. However, despite this challenge, the gastrointestinal tract is rarely colonized by microbial pathogens, suggesting that it has effective innate and systemic defense systems. Goblet cells, epithelial cells, macrophages, and dendritic cells are the main cellular components of the innate defense system, and the mucus layer, which contains mucins, is the front line of this system [ 5 , 8 ]. T and B cells are the main combatants of the adaptive immune system, providing the final line of defense both as master regulators and as an inducible system to eliminate pathogens that have bypassed innate lines of defense. In various intestinal infections caused by bacteria, viruses and parasites, an association with changes in goblet cell response and mucin production is observed [2, 9, 10]. In addition, quantitative and qualitative changes in mucins are observed in other gastrointestinal diseases such as ulcerative colitis [11], colon carcinoma [12] and celiac disease [13]. In conclusion, there is now considerable evidence indicating an important role for goblet cells and mucins in various GI disorders, and a precise understanding of goblet cell biology and the function of mucins in pathology, pathophysiology and host defense in the gastrointestinal tract is essential.

What Is The Function Of Goblet Cells

In the gastrointestinal tract, goblet cells, as well as three other principal cells (enterocytes, enteroendocrine cells, and Paneth cells), arise from a multipotent stem cell located near the base of the crypts of Lieberkühn [14]. It is currently believed that progenitor cells within the proliferative compartment arise from these stem cells and, leaving the crypts, further differentiate into each intestinal cell lineage [ 15 , 16 ]. Goblet cells appear early in development (in the human fetal small intestine, 9–10 weeks of gestation) and their morphology is shaped by an enlarged theca containing mucin granules located below the apical membrane [17]. A kinetic analysis of goblet cell dynamics in mouse intestine shows that proliferated goblet cells migrate from the base of the crypt to the tip of the villi, where they enter the lumen [18]. This progression from birth to death occurs in mice within 2–3 days; thus, the goblet cell population is short-lived and constantly changing. Goblet cells undergo dramatic morphological changes during their lifetime. As shown by morphometric studies of the rabbit colon [19], after proliferation from stem cells at the base of the crypt, immature goblet cells begin to rapidly synthesize and secrete mucin granules. These crypt-based immature goblet cells are large and pyramidal in shape, and as the cell progresses toward the surface of the colon, it decreases in volume, shedding cytoplasm and organelles trapped between mucin granules as the granules are released. During this volume reduction, cell morphology changes; the contact with the lumen increases, the organelles separate. At the mouth of the crypt, the cell takes on its characteristic cup shape; the apical part of the cell is elongated and packed with mucin granules, while the basal part of the cell tapers to a cup-like “stem” containing the nucleus and synthetic organelles. Although goblet cells are distributed throughout the length of the mammalian gastrointestinal tract, their contribution to the total epithelial volume is not constant. In the rat small intestine, goblet cell volume density increases aborally, from the duodenum to the distal ileum [5]. This trend continues in the large intestine, and colonic epithelial goblet cell density also increases from proximal to distal, from the cecum to the rectum. The maintenance and differentiation of stem cells into specific cell lineages in the intestine involves a complex interaction of several developmental pathways, including Wnt/β-catenin, bone morphogenic protein (BMP), and PI3-kinase/Akt signaling [ 20 ]. The basic helix-loop-helix (bHLH) gene Math1 is a homologue of the mammalian Drosophila atonal gene and is expressed in the gastrointestinal tract during development and has been identified in both immature crypts and intestinal epithelial villi [21]. Math1 appears to be important for the specification of intestinal secretory lineages, as Math1-deficient mice fail to develop three of the four cell types of the GI mucosa—goblet, Paneth, and enteroendocrine cells.

Intestinal Goblet Cells Sample And Deliver Lumenal Antigens By Regulated Endocytic Uptake And Transcytosis

Intestinal mucus is a highly hydrated aggregate that serves as the primary line of innate host defense against endogenous and exogenous stimuli, microbial attachment, and invasion, yet allows nutrient transport. Mucins act as the main structural component of the intestinal mucus layer and are mainly secreted by goblet cells, which are dispersed throughout the epithelial layer. Mucins are the main polymeric, viscous and protective components of mucus. In addition to mucins, mucus consists of water, ions, and molecules of the immune system, such as immunoglobulin A (IgA) and antimicrobial peptides, which facilitate the elimination of pathogenic organisms [22, 23, 24, 25, 26] .

Daltons [27], which assemble into a protective gel-like layer that extends up to 150 μm of the epithelial surface [28]. Mucin glycoproteins consist of linear or branched oligosaccharide chains attached to a protein core with a very different amino acid composition. Serine (Ser) and threonine (Thr) are even more common in major proteins, accounting for 41% of the molecule in humans [29] and 57% in rats [30] . Both Ser and Thr have side chains that contain a hydroxyl

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