Endoglin and VEGF overexpression in colonic mucosa of patients with ulcerative colitis - possible therapeutical target

Author(s):  
Cristiana Popp
2012 ◽  
Vol 302 (10) ◽  
pp. G1163-G1170 ◽  
Author(s):  
Kazuhiko Uchiyama ◽  
Yuji Naito ◽  
Tomohisa Takagi ◽  
Katsura Mizushima ◽  
Yasuko Hirai ◽  
...  

Serpin B1 is a monocyte neutrophil elastase (NE) inhibitor and is one of the most efficient inhibitors of NE. In the present study, we investigated the role of serpin B1 in the pathogenesis of ulcerative colitis by using clinical samples and an experimental model. The colonic expression of serpin B1 was determined by real-time polymerase chain reaction (PCR), Western blot analysis, and immunohistological studies in both normal and inflamed mucosa from patients with ulcerative colitis. Serpin B1 mRNA expression was determined by real-time PCR in the mouse dextran sodium sulfate (DSS)-induced colitis model. Young adult mouse colonic epithelial (YAMC) cells were used to determine the role of serpin B1. Serpin B1 gene transfected YAMC cells were treated with H2O2 to measure cell viability. The expression of NE was determined in YAMC cells treated with H2O2. NE-silenced YAMC cells were also treated with H2O2 and then measured for viability. Upregulated expression of serpin B1 in colonic mucosa was confirmed from patients with active ulcerative colitis. Immunohistochemical studies showed that serpin B1 expression was localized not only in inflammatory infiltration cells but also in epithelial cells. Serpin B1 mRNA expression was also increased in colonic mucosa of mouse DSS-induced colitis. Serpin B1-transfected YAMC cells were resistant against the treatment of H2O2. H2O2 treatment significantly induced NE in YAMC cells, and NE-silenced YAMC cells were also resistant against the treatment of H2O2. These results suggest that serpin B1 may be a novel marker of active ulcerative colitis and may play an important role in the pathogenesis of inflammatory bowel disease.


2002 ◽  
Vol 17 (8) ◽  
pp. 849-853 ◽  
Author(s):  
Toshifumi Ohkusa ◽  
Nobuhiro Sato ◽  
Tatuo Ogihara ◽  
Koji Morita ◽  
Masayuki Ogawa ◽  
...  

2004 ◽  
Vol 91 (5) ◽  
pp. 715-723 ◽  
Author(s):  
Yajun Cheng ◽  
Lena Ohlsson ◽  
Rui-Dong Duan

Dietary fibre and fat affect colonic tumourigenesis and inflammation. Sphingomyelin metabolism may have implications for the pathogenesis of colonic tumours and ulcerative colitis. The present study examined the effects of psyllium and fat on the enzymes responsible for sphingomyelin metabolism and apoptosis in the colon. Mice were fed control, psyllium-containing (100 g/kg), high-fat (313 g/kg, 53 % energy as fat) or high-fat plus psyllium diets for 4 weeks. The activities of acid, neutral and alkaline sphingomyelinase (SMase), neutral ceramidase, and caspase 3, 8 and 9 in colonic mucosa were determined. The expressions of alkaline SMase and caspase 3 were examined. The psyllium-containing diet was found to increase significantly the activities of alkaline SMase and caspase 3 and decreased those of acid SMase and neutral ceramidase. The high-fat diet had opposite effects on these enzymes and attenuated the effects of psyllium. Western blotting showed that psyllium increased and high-fat decreased the levels of alkaline SMase and caspase 3 in colonic mucosa. The change in caspase 3 activity was positively correlated with that of alkaline SMase and negatively with acid SMase. No similar changes of acid and alkaline phosphatase activities in the colon or acid and neutral SMase activity in the liver were identified. In conclusion, colonic sphingomyelin metabolism and apoptosis were affected by psyllium and fat in an opposite manner. The results may have implications for colorectal tumourigenesis and inflammation.


2013 ◽  
Vol 144 (5) ◽  
pp. S-825
Author(s):  
Franck Carbonero ◽  
Ann C. Benefiel ◽  
Jona Kristo ◽  
Jenna K. Leinberger ◽  
Maeve M. Leurck ◽  
...  

Author(s):  
Yasuo Takahashi ◽  
Hideki Masuda ◽  
Yukimoto Ishii ◽  
Yayoi Nishida ◽  
Megumi Kobayashi ◽  
...  

Epigenomics ◽  
2021 ◽  
Author(s):  
Bing Li ◽  
Yan Li ◽  
Lixiang Li ◽  
Yu Yu ◽  
Xiang Gu ◽  
...  

Aims: Few circRNAs have been thoroughly explored in ulcerative colitis (UC). Materials & methods: Microarrays and qualitative real-time PCR were used to detect and confirm dysregulated circRNAs associated with UC. Functional analysis was performed to explore the roles. Results: A total of 580 circRNAs and 87 miRNAs were simultaneously dysregulated in both inflamed and noninflamed UC colonic mucosa compared with healthy controls. Accordingly, hsa_circ_0001021 was significantly downregulated in patients with UC and was related to Mayo scores. Clinical samples and cell experiments revealed that hsa_circ_0001021 was expressed in epithelial cells and correlated with ZO-1, occludin and CLDN-2. Moreover, hsa_circ_0001021 sponged miR-224-5p to upregulate smad4 and increased ZO-1 and occludin. Conclusion: Hsa_circ_0001021 is related to UC severity and regulates epithelial barrier function via sponging miR-224-5p.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S289-S289
Author(s):  
S Yamada ◽  
S Yamamoto ◽  
Y Honzawa ◽  
Y Hayashi ◽  
H Kitamoto ◽  
...  

Abstract Background Cytomegalovirus (CMV) and Epstein–Barr virus (EBV) are members of the herpesvirus family. CMV reactivation is often complicated with ulcerative colitis (UC) and is known as one of exacerbation factors. However, the association between EBV reactivation and pathophysiology of UC is still unclear. Methods This study enrolled 116 active UC patients who received colonoscopy between January 2005 and January 2019 in Kyoto University Hospital. 244 biopsy specimens were obtained from inflamed colonic mucosa to assess EVB and CMV reactivation. Viral loads of EBV and CMV in inflamed mucosa were measured by real-time PCR assay. The reactivation of those viruses was defined as DNA quantity more than 10 copies/μg DNA. Clinical severity was assessed by Lichtiger index and defined as follow: 4–8 as mild, 9–12 as moderate, and more than 12 as severe. Endoscopic severity was assessed by Mayo endoscopic score. We examined the correlation between the positivity of each viral reactivation and patients’ characteristics or prognosis of UC. Results (1) Median age, Lichtiger score and Mayo endoscopic score at the time to assess the viral reactivations were 36 years-old, 8, and 3, respectively. (2) EBV and CMV reactivation were observed in 127 samples (52.0%) and 73 samples (29.9%), respectively. There was no correlation between EBV and CMV viral load (correlation coefficient 0.19), although a significant correlation between those viral reactivations was observed in active colonic mucosa of UC patients (p = 0.002). (3) The proportion of EBV reactivation was higher in both clinically and endoscopically severe UC patients compared with those with mild activity. On the other hands, there was no association between CMV reactivation and clinical or endoscopic severity. (4) Multivariate analysis indicated risk factors for EBV reactivation as receiving anti-TNF-α antibodies (odds ratio [OR] 4.2) or calcineurin inhibitors (OR 3.5), and CMV reactivation (OR 2.1), respectively. (5) Multivariate analysis also indicated risks for CMV reactivation as steroid-refractory (OR 4.7) and EBV reactivation (OR 2.0). (6) EBV and CMV reactivation did not affect clinical outcomes including the requirement of colectomy or intensification of immunosuppressive treatments and the incidence of colitis-associated cancer, dysplasia and lymphoproliferative disease. Conclusion Reactivation of EBV or CMV may behave differently in pathophysiology of UC. Further studies are required to clarify the role of EBV reactivation on colonic inflammation in UC patients.


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