TY - JOUR
T1 - Urine-based detection of intestinal tight junction loss.
AU - Thuijls, G.
AU - Derikx, J.P.
AU - de Haan, J.J.
AU - Grootjans, J.
AU - de Bruine, A.
AU - Masclee, A.A.
AU - Heineman, E.
AU - Buurman, W.A.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - BACKGROUND: Tight junction breakdown, with loss of the important sealing protein claudin-3, is an early event in the development of intestinal damage. Therefore, noninvasive analysis of intestinal tight junction status could be helpful in early detection of intestinal injury. AIM: To investigate the usefulness of urinary claudin-3 as marker for intestinal tight junction loss. METHODS: A rat hemorrhagic shock model and a human setting of known intestinal damage, that is, patients with relapsed inflammatory bowel disease (IBD), were used to investigate intestinal tight junction status by immunohistochemical staining and urinary claudin-3 levels by western blot. RESULTS: In rats claudin-3 urine levels increased rapidly after histologically proven intestinal tight junction loss, with significantly elevated levels at 90 minutes after shock compared with sham-operated animals [mean+/-SEM: 611+/-101 intensity (INT), n=6 vs. 232+/-30 INT, n=6; P<0.05]. Moreover, in colonic biopsies of patients with IBD relapse claudin-3 staining was reduced compared with biopsies of patients with IBD without signs of disease. Concomitantly, significantly increased claudin-3 urine levels were found in these patients (502+/-67 INT, n=10) compared with patients with IBD in remission (219+/-17 INT, n=10, P<0.001) and healthy volunteers (225+/-38 INT, n=10, P<0.001). CONCLUSION: Here we show for the first time in both an experimental and clinical setting a strong relation between intestinal tight junction loss and urinary claudin-3 levels. These findings suggest that measurement of urinary claudin-3 can be used as noninvasive marker for intestinal tight junction loss. This offers new opportunities for early diagnosis and follow-up of intestinal injury.
AB - BACKGROUND: Tight junction breakdown, with loss of the important sealing protein claudin-3, is an early event in the development of intestinal damage. Therefore, noninvasive analysis of intestinal tight junction status could be helpful in early detection of intestinal injury. AIM: To investigate the usefulness of urinary claudin-3 as marker for intestinal tight junction loss. METHODS: A rat hemorrhagic shock model and a human setting of known intestinal damage, that is, patients with relapsed inflammatory bowel disease (IBD), were used to investigate intestinal tight junction status by immunohistochemical staining and urinary claudin-3 levels by western blot. RESULTS: In rats claudin-3 urine levels increased rapidly after histologically proven intestinal tight junction loss, with significantly elevated levels at 90 minutes after shock compared with sham-operated animals [mean+/-SEM: 611+/-101 intensity (INT), n=6 vs. 232+/-30 INT, n=6; P<0.05]. Moreover, in colonic biopsies of patients with IBD relapse claudin-3 staining was reduced compared with biopsies of patients with IBD without signs of disease. Concomitantly, significantly increased claudin-3 urine levels were found in these patients (502+/-67 INT, n=10) compared with patients with IBD in remission (219+/-17 INT, n=10, P<0.001) and healthy volunteers (225+/-38 INT, n=10, P<0.001). CONCLUSION: Here we show for the first time in both an experimental and clinical setting a strong relation between intestinal tight junction loss and urinary claudin-3 levels. These findings suggest that measurement of urinary claudin-3 can be used as noninvasive marker for intestinal tight junction loss. This offers new opportunities for early diagnosis and follow-up of intestinal injury.
U2 - 10.1097/MCG.0b013e31819f5652
DO - 10.1097/MCG.0b013e31819f5652
M3 - Article
C2 - 19525861
SN - 0192-0790
VL - 44
SP - e14-19
JO - Journal of Clinical Gastroenterology
JF - Journal of Clinical Gastroenterology
IS - 1
ER -