scholarly journals The ulcerative colitis associated gene FUT8 regulates the quantity and quality of secreted mucins

2021 ◽  
Author(s):  
Gerard Cantero ◽  
Carla Burballa ◽  
Yuki Ohkawa ◽  
Tomohiko Fukuda ◽  
Yoichiro Harada ◽  
...  

Fucosylation of mucins, the main macrocomponents of the mucus layer that protects the digestive tract from pathogens, increases their viscoelasticity and shear stress resistance. These properties are altered in patients with ulcerative colitis (UC), which is marked by a chronic inflammation of the distal part of the colon. Here we show that the levels of Fucosyltransferase 8 (FUT8) and specific mucins are increased in the distal inflamed colon of UC patients compared to normal individuals. Overexpressing FUT8, as observed in UC, in mucin-producing HT29-18N2 colonic cell line increases trafficking of MUC1 to plasma membrane and secretion of MUC2/MUC5AC. FUT8 depletion (FUT8 KD), instead, causes intracellular accumulation of MUC1 and alters the ratio of secreted MUC2 to MUC5AC. Mucins secreted by FUT8 overexpressing cells are more resistant to shear stress compared to mucins secreted by FUT8 KD cells. These data fit well with the Fut8-/- mice phenotype, which are protected against UC. Fut8-/- mice exhibit a thinner proximal colon mucus layer with an altered ratio of neutral to acidic mucins compared to Fut8+/+ mice. Together, these data reveal that FUT8 optimizes the viscoelastic properties of the extracellular mucous by controlling the quantities of mucins secreted.

Medicine ◽  
2017 ◽  
Vol 96 (16) ◽  
pp. e6651 ◽  
Author(s):  
Yan-Cheng Dai ◽  
Lie Zheng ◽  
Ya-Li Zhang ◽  
Xuan Chen ◽  
De-Liang Chen ◽  
...  

1993 ◽  
Vol 7 (7) ◽  
pp. 411-416 ◽  
Author(s):  
Andreas Ludwig ◽  
Ralf Weidemann ◽  
J�rg Tomeczkowski ◽  
Gerlinde Kretzmer

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Jason A. Randall ◽  
Aiste Guobyte ◽  
Laure Delbecque ◽  
Louise Newton ◽  
Tara Symonds ◽  
...  

Abstract Background Ulcerative Colitis (UC) is a chronic gastrointestinal disease that often presents during one’s most productive years and is characterized by colon inflammation. Key symptoms and impacts in adults are well-known, however, experiences among pediatric populations have not been well documented. The purpose of this study was to understand the health-related quality of life and symptomatic experience of children (2–11 years) living with UC. Methods Qualitative, semi-structured face-to-face interviews were conducted. Children aged 5–11 years were interviewed, as well as their parents/caregivers in matched dyads. Parents/caregivers of children aged2–4 years were interviewed within a parent/caregiver-only cohort. All participants were recruited from the United States. Interviews were coded using thematic analysis. Results Key symptoms and impacts reflecting the lived experience of UC were identified following thematic analysis, generating a conceptual model. A total of 32 participants (20 parents/caregivers and 12 children) were interviewed. Results identified a substantial burden of UC in children. All children and parents/caregivers reported that they/their child experienced stomach/abdominal pain. Other symptoms discussed by over 75% were blood in stool, diarrhea/loose stools, stool urgency, incomplete evacuation, stool frequency, and feeling gassy/passing gas. The most frequently discussed impacts by over 75% of participants were on emotional and practical aspects, seriously affecting quality of life. Conclusions Qualitative analysis of the interviews identified a substantial burden of UC on children, with a profound impact on their lives. The symptomatic experience is reflective of adults and adolescents. A high level of agreement between parents/caregivers and children was demonstrated regarding the perception of the presence or absence of symptoms. Children aged 8–11 years showed higher levels of agreement with parents/caregivers than did younger children, indicating appropriateness of self-report of symptom data in the 8–11 years age group.


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