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Regulation and Targeting of MUCINS in Pancreatic Cancer
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Shailendra K. Gautam, Abhijit Aithal, Grish C. Varshney, Parthasarathy Seshacharyulu
Mucins are family of high molecular weight glycoproteins that have been reported to play a structural and functional role in PC pathogenesis. Both secretory mucins e.g. MUC2, MUC5AC, MUC5B, MUC6–9, and MUC19 and membrane-bound mucins e.g. MUC1, MUC3A/B, MUC4, MUC11–13, MUC15–17, and MUC20–22 have clinical significance as predictive biomarkers for disease progression and as putative therapeutic targets [14, 19]. Importantly, MUC1, MUC4, MUC5AC, and MUC16 have been thoroughly investigated for their role in PC progression [14, 20]. However, more efforts need to be directed towards the optimization of mucin-based therapeutic approaches in PC. Strategically, mucin-based diagnostic and therapeutic approaches can be divided based on their secretory and membrane-bound nature. For instance, the membrane-bound mucins like MUC1, MUC4, and MUC16 are more suitable for targeted therapies including small molecule inhibitors, antibody-based therapy, and other vaccine-based immunotherapy. In contrast, the secretory mucins MUC2 and MUC5AC are more likely to have potential as biomarkers. This chapter will highlight the significant findings related to transmembrane mucins such as MUC1, MUC 4 and MUC16 due to their well-characterized structure and biological functions. Further, the mucin-based targeting approach will emphasize the global perspective to delineate the therapeutic potentials of different membrane bound mucins in PC.
Bile Acids in the Pathogenesis of Necrotizing Enterocolitis
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Mucins form a semipermeable protective layer between the intestinal lumen and epithelium (74). Deficiencies in MUC2 production by goblet cells may contribute to intestinal damage in NEC (75, 76), and when neonatal rats subjected to the NEC protocol were treated with cholestyramine to sequester luminal BAs, the diminished Muc2 observed in NEC was normalized (77). BAs have been shown to affect secretion (78) and up-regulation of MUC2 (79) in human cell lines. In ileal explants from neonatal rats, BAs decreased Muc2-positive cells, likely by inducing secretion (77). Interestingly, BA culture did not have the same effect on ileal explants from adult rats, suggesting neonatal intestine may be inherently more susceptible to BA-induced damage.
Rhinitis
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Vinay Mehta, Srinivasan Ramanuja, Pramod S Kelkar
Nasal mucus acts as a barrier against external pathogens and has antioxidant, antiprotease and antimicrobial properties. Major constituents of nasal mucus are the mucins, which play an important role in antimicrobial and anti-inflammatory defenses and in mucociliary clearance. Ciliated epithelium traps foreign bodies in a thin layer of surface mucus that migrates towards the posterior nasopharynx.
Prebiotic oligofructose protects against high-fat diet-induced obesity by changing the gut microbiota, intestinal mucus production, glycosylation and secretion
Published in Gut Microbes, 2022
Paola Paone, Francesco Suriano, Ching Jian, Katri Korpela, Nathalie M. Delzenne, Matthias Van Hul, Anne Salonen, Patrice D. Cani
It has been observed that during obesity and metabolic disorders the gut microbiota composition is different and this is associated with gut barrier dysfunction.3,4 Among the components of the gut barrier, the mucus layer is critical and hence has raised more attention in recent years. The mucus layer is the first line of protection of the gastrointestinal tract and the interface of communication between the gut microbiota and the host.5 It is produced and secreted by the goblet cells and mainly composed of specific proteins called mucins. Mucins are heavily glycosylated proteins with different glycans, often representing more than 80% of the mucin mass.5 The enzymes responsible for the mucin glycosylation are called glycosyltransferases and are specific for each glycan residue and for precise positions. The mucins are classified as secreted and transmembrane and the most important component of the mucus layer is the secreted mucin 2 (Muc2).
Impact of quorum sensing signaling molecules in gram-negative bacteria on host cells: current understanding and future perspectives
Published in Gut Microbes, 2022
Yingping Xiao, Huicong Zou, Jingjing Li, Tongxing Song, Wentao Lv, Wen Wang, Zhenyu Wang, Shiyu Tao
The gut<apos;>s first line of defense against invasion of pathogenic microorganisms and harmful metabolites is the mucus layer that covers the outer side of intestinal epithelial cells.145,146 The main component of the mucus layer is mucin, which is synthesized and secreted by intestinal goblet cells and acts as a barrier covering the entire intestinal surface.147–149 Studies have shown that the absence or abnormal expression of mucins can lead to intestinal diseases, whereas pathogenic microorganisms and some of their metabolites can induce abnormal expression of mucins.150–152 As for the influence of AHL on the intestinal mucus barrier, we first established a co-culture model of 3-oxo-C12-HSL and intestinal goblet cells, and demonstrated that 3-oxo-C12-HSL induced an imbalance of intestinal goblet cell homeostasis by causing mitochondrial swelling, mitochondrial membrane potential depolarization, mitochondrial dysfunction, and cell apoptosis. Furthermore, 3-oxo-C12-HSL inhibits mucin synthesis and sulfuration, ultimately destroying the intestinal mucus barrier. On this basis, the 3-oxo-C12-HSL/PON2 specific inhibitor/intestinal goblet cell co-culture model was established, and it was found that 3-oxo-C12-HSL induced a series of harmful biological effects in a PON2-dependent manner, eventually resulting in the disorder of intestinal goblet cell structure and function 85,153,154 (Figure 3).
Identification of novel adhesive proteins in pearl oyster by proteomic and bioinformatic analysis
Published in Biofouling, 2021
Mucins (IPR023217) are a family of high molecular weight, heavily-glycosylated proteins produced by epithelial tissues in most organisms. The key characteristic of mucins is their ability to form gels. In addition, mucins can serve a variety of functions ranging from lubrication to cell signaling (Hollingsworth and Swanson 2004). Three mucin-like proteins were found in the adhesive plaques (Table 1 and Figure S5). Interestingly, mucin-like proteins were found in sea star adhesive footprints and could be involved in the formation of structural networks through oligomerization and/or crosslinking with other adhesive proteins (Hennebert et al. 2015). Although adhesives were thoroughly cleaned with water before analysis, mucin-like proteins might be contaminants from the mucus of the foot, which need to be tested by immunohistochemistry experiments in the future.