scholarly journals Sex- and Age-Related Estrogen Signaling Alteration in Inflammatory Bowel Diseases: Modulatory Role of Estrogen Receptors

2019 ◽  
Vol 20 (13) ◽  
pp. 3175 ◽  
Author(s):  
Damian Jacenik ◽  
Adam I. Cygankiewicz ◽  
Anna Mokrowiecka ◽  
Ewa Małecka-Panas ◽  
Jakub Fichna ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Inflammatory Bowel Diseases ◽  
Protein Level ◽  
Estrogen Signaling ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Age Related ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The pathogenesis of inflammatory bowel diseases (IBD) seems to be associated with alterations of immunoregulation. Several lines of evidence suggest that estrogens play a role in the modulation of immune responses and may be related to the etiology of IBD. The purpose of this work was to examine the involvement of G protein-coupled estrogen receptor (GPER), estrogen receptor α (ERα), estrogen receptor β (ERβ) and ERα spliced variants ERα36 and ERα46 in Crohn’s disease (CD) and ulcerative colitis (UC). The studied group included 73 patients with IBD and 31 sex and age-related controls. No differences in serum levels of 17β-estradiol nor of CYP1A1 and SULT1E1 enzymes involved in estrogen catabolism were stated. The expression pattern of estrogen receptors in tissue samples was quantified using real-time PCR and Western blotting. Statistically significant up-regulation of GPER and ERα in both CD and UC as well as down-regulation of ERβ in CD patients was found. However, differences in the expression of estrogen receptors in CD and UC have been identified, depending on the sex and age of patients. In men, up-regulation of GPER, ERα and ERα46 expression was shown in CD and UC patients. In women under 50 years of age, GPER protein level increased in UC whereas ERβ expression tended to decrease in CD and UC patients. In turn, in women over 50 the protein level of ERα increased in UC while ERβ expression decreased in CD patients. Dysregulation of estrogen receptors in the intestinal mucosa of patients with CD and UC indicates that estrogen signaling may play a role in the local immune response and maintain epithelial homeostasis in a gender- and age-dependent manner.

scholarly journals P163 Changes in diagnostic delay in inflammatory bowel diseases over the years: a retrospective single-centre analysis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S220-S220
Author(s):  
M Di Ruscio ◽  
F Vernia ◽  
A Variola ◽  
G Lunardi ◽  
S Resimini ◽  
...  
Keyword(s):  
Median Time ◽  
Inflammatory Bowel Diseases ◽  
Biological Treatment ◽  
Diagnostic Delay ◽  
Delayed Diagnosis ◽  
Age Related ◽  
Time To Diagnosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Difference

Abstract Background Delayed diagnosis is common in inflammatory bowel diseases (IBD) and has been reported to be longer for patients with Crohn’s disease (CD) than for those with ulcerative colitis (UC). Aims of study were to assess the median time to diagnosis in IBD patients, to examine whether diagnostic delay (DD) has improved over the years and its impact on biological treatment and need for surgery. Methods A retrospective monocentric study including IBD patients living in the area of Verona (Italy), diagnosed up to 2019 and followed-up for at least 6 months at IRCCS Sacro Cuore—Don Calabria, Negrar, was carried out. DD was defined as the period (months) from symptoms onset to histological diagnosis of IBD and reported as <6 months, 6–12 months and >12 months. Results Six-hundred-six patients (255 CD; 351 UC; 308 males; 298 females) were enrolled. Median DD was 10 (IQR 2–12), 6 (IQR 1–12) and 2 (IQR 1–7) months <2000, between 2001–2010, and >2010, respectively. Median time to diagnosis was not significantly longer in CD than in UC patients (4 vs. 3 months; IQR 1- 12). No sex- or age-related differences in DD were observed. Using the Mann–Whitney test, DD was longer in patients diagnosed <2000 and between 2001–2010, than in those diagnosed >2010 (p = 0.0000 and p = 0.0004). Comparing DD <2000 and >2010, the statistical difference was reported for UC (p = 0.0000) but not for CD (p = 0.2756). Considering the use of biologics over the years, patients diagnosed between 2000–2010, and >2010 were compared (194 CD and 333 UC), reporting a significant increase in their use both for CD (30 vs. 60; p = 0.0008) and UC (28 vs. 43; p = 0.0000). DD did not influence the need for biological treatment in both diseases (p = 0.987 for CD; p = 0.433 for UC). Considering a DD <6, 6–12, and >12 percentages of patients needing biologics were respectively 53.4%, 63.6% and 56.5% for CD and 28.5%, 34.1% and 26.3% for UC. Seventy-two CD and 27 UC patients needed surgery. Analyzing the time to surgery, DD did not influence the rate of resections in CD (p = 0.6559), as well as in UC (p = 0.2792). Conclusion In our cohort, DD has significantly decreased over the last years, more for UC than CD patients. This is probably related to the increased awareness of patients on disease and of general practitioners in sending them to the specialist. Considering the published literature, UC and CD did not differ in DD; moreover age at diagnosis did not affect DD in our patients. DD did not influence the need for biological treatment or surgery rates in both diseases. These results are probably related to the difference in disease extension and severity among the patients enrolled. An analysis on targeted patients at higher risk for bowel damage is presently under way.

scholarly journals Expressions of Matrix Metalloproteinases (MMP-2, MMP-7, and MMP-9) and Their Inhibitors (TIMP-1, TIMP-2) in Inflammatory Bowel Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Katarzyna Jakubowska ◽  
Anna Pryczynicz ◽  
Piotr Iwanowicz ◽  
Andrzej Niewiński ◽  
Elżbieta Maciorkowska ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Bowel Diseases ◽  
Inflammatory Infiltration ◽  
Tissue Samples ◽  
Metalloproteinase Inhibitors ◽  
Bowel Diseases ◽  
Tissue Changes ◽  
Inflammatory Bowel

Crohn’s disease (CD) and ulcerative colitis (UC) belong to a group of inflammatory bowel diseases (IBD). The aim of our study was to evaluate the expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 in ulcerative colitis and Crohn’s disease. The study group comprised 34 patients with UC and 10 patients with CD. Evaluation of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 expression in tissue samples was performed using immunohistochemistry. The overexpression of MMP-9 and TIMP-1 was dominant in both the glandular epithelium and inflammatory infiltration in UC patients. In contrast, in CD subjects the positive expression of MMP-2 and TIMP-1 was in glandular tubes while mainly MMP-7 and TIMP-2 expression was in inflammatory infiltration. Metalloproteinases’ expression was associated with the presence of erosions, architectural tissue changes, and inflammatory infiltration in the lamina propria of UC patients. The expression of metalloproteinase inhibitors correlated with the presence of eosinophils and neutrophils in UC and granulomas in CD patients. Our studies indicate that the overexpression of metalloproteinases and weaker expression of their inhibitors may determine the development of IBD. It appears that MMP-2, MMP-7, and MMP-9 may be a potential therapeutic target and the use of their inhibitors may significantly reduce UC progression.

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