Mucin Expression Profiles in Ulcerative Colitis: New Insights on the Histological Mucosal Healing

被引:5
作者
Leoncini, Giuseppe [1 ]
Cari, Luigi [2 ]
Ronchetti, Simona [2 ]
Donato, Francesco [3 ]
Caruso, Laura [4 ]
Calafa, Cristina [4 ]
Villanacci, Vincenzo [5 ]
机构
[1] Fdn IRCCS Ist Nazl Tumori, Dept Pathol & Lab Med, Pathol Div 1, I-20133 Milan, Italy
[2] Univ Perugia, Dept Med & Surg, Pharmacol Div, I-06132 Perugia, Italy
[3] Univ Brescia, Unit Hyg Epidemiol & Publ Hlth, I-25123 Brescia, Italy
[4] Desenzano Garda Hosp, Dept Pathol & Lab Med, Pathol Unit, I-25015 Brescia, Italy
[5] ASST Spedali Civili, Inst Pathol, I-25123 Brescia, Italy
关键词
ulcerative colitis; mucosal healing; mucins; mucus barrier; mucin enhancer; GENE-EXPRESSION; RETINOIC ACID; BUTYRATE; CELLS; BARRIER; INFLAMMATION; INDUCTION; SECRETION; ECOSYSTEM;
D O I
10.3390/ijms25031858
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A structural weakness of the mucus barrier (MB) is thought to be a cause of ulcerative colitis (UC). This study aims to investigate the mucin (MUC) composition of MB in normal mucosa and UC. Ileocolonic biopsies were taken at disease onset and after treatment in 40 patients, including 20 with relapsing and 20 with remitting UC. Ileocolonic biopsies from 10 non-IBD patients were included as controls. Gut-specific MUC1, MUC2, MUC4, MUC5B, MUC12, MUC13, MUC15, and MUC17 were evaluated immunohistochemically. The promoters of mucin genes were also examined. Normal mucosa showed MUC2, MUC5B, and MUC13 in terminal ileum and colon, MUC17 in ileum, and MUC1, MUC4, MUC12, and MUC15 in colon. Membranous, cytoplasmic and vacuolar expressions were highlighted. Overall, the mucin expression was abnormal in UC. Derangements in MUC1, MUC4, and MUC5B were detected both at onset and after treatment. MUC2 and MUC13 were unaffected. Sequence analysis revealed glucocorticoid-responsive elements in the MUC1 promoter, retinoic-acid-responsive elements in the MUC4 promoter, and butyrate-responsive elements in the MUC5B promoter. In conclusion, MUCs exhibited distinct expression patterns in the gut. Their expression was disrupted in UC, regardless of the treatment protocols. Abnormal MUC1, MUC4, and MUC5B expression marked the barrier dysfunction in UC.
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页数:15
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