Hepatocyte growth factor (HGF) modulates intestinal epithelial cell proliferation and migration, serving as a critical regulator of intestinal wound healing. In this study, we examined the effect of administration of recombinant human HGF on colonic mucosal damage in vivo. Acute colitis was induced in rats by feeding with 5% dextran sulfate sodium (DSS) for 7 days, and colitis was subsequently maintained by feeding with 1% DSS. On the 5th day of DSS administration, osmotic pumps releasing recombinant human HGF (200 g/day) were implanted into the peritoneum of the rats. Continuous intraperitoneal delivery of HGF led to both increased serum human HGF levels and c-Met tyrosine phosphorylation within the colonic mucosa. Compared with mock-treated rats, those administered human HGF showed a reduction in colitis-associated weight loss, large intestinal shortening, and improved colonic erosions. Enhanced epithelial regeneration and cellular proliferation were observed in rats treated with recombinant human HGF. The weights of the liver, kidneys, and spleen were not affected by HGF administration. These results indicate that HGF administration accelerates colonic mucosal repair in rats with DSS-induced colitis and suggest that recombinant human HGF may be a useful therapeutic tool to facilitate intestinal wound healing in patients with ulcerative colitis.

This retrospective evaluation found that endoscopic closure was associated with a reduced risk of delayed bleeding after duodenal ESD. Delayed bleeding after duodenal ESD might be prevented by prophylactic endoscopic closure.

Background Peritoneal dialysis (PD) is a common treatment for patients with reduced or absent renal function. Long-term PD leads to peritoneal injury with structural changes and functional decline, such as ultrafiltration loss. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis, a serious complication of PD. Glucose degradation products contained in PD fluids contribute to the bioincompatibility of conventional PD fluids. Methylglyoxal (MGO) is an extremely toxic glucose degradation product. The present study examined the injurious effect of MGO on peritoneum in vivo. Methods Male Sprague–Dawley rats ( n = 6) were administered PD fluids (pH 5.0) containing 0, 0.66, 2, 6.6, or 20 mmol/L MGO every day for 21 days. On day 22, peritoneal function was estimated by the peritoneal equilibration test. Drained dialysate was analyzed for type IV collagen-7S, matrix metalloproteinase (MMP), and vascular endothelial growth factor (VEGF). Histological analysis was also performed. Results In rats receiving PD fluids containing more than 0.66 mmol/L MGO, peritoneal function decreased significantly and levels of type IV collagen-7S and MMP-2 in drained dialysate increased significantly. In the 20-mmol/L MGO-treated rats, loss of body weight, expression of VEGF, thickening of the peritoneum, and formation of abdominal cocoon were induced. MMP-2 and VEGF were produced by infiltrating cells in the peritoneum. Type IV collagen was detected in basement membrane of microvessels. Conclusion MGO induced not only peritoneal injury but also abdominal cocoon formation in vivo. The decline of peritoneal function may result from reconstitution of microvessel basement membrane or neovascularization.

These results indicate that intravenous injection of HGF accelerates colonic mucosal repair and reduces infiltration of inflammatory cells in rats with TNBS-induced colitis and suggest that HGF has the potential to be a new therapeutic modality to promote intestinal mucosal repair in patients with inflammatory bowel disease.

IntroductionElectrophysiological techniques were used to determine the electrical properties of the collecting duct (CD) cell in the isolated cortical collecting duct from obstructed (UUOOK) and contralateral (UUOcK) kidneys in rabbits 24 h after unilateral ureteral obstruction (UUO); results were compared with those from sham-operated kidneys. The lumen-negative transepitheHal voltage and the basolateral membrane voltage (V B) were decreased in the UUOOK, and increased in the UUOCK. The transepithelial conductance (GT) was decreased in parallel with an increase in the fractional apical membrane resistance (fRA) and a decrease in apical membrane conductance in the UUOOK. By contrast, the GT was increased in parallel with increases in apical and basolateral membrane conductances in the UUOCK. The amiloride-sensitive changes in apical membrane voltage (V A), GT and f RA were lower in the UUOOK, but greater in the UUOCK. The changes in V A and GT upon raising the perfusate K+ concentration and upon addition of luminal Ba2" were decreased in the UUOOK, and increased in the UUOCK. Addition of ouabain to the bath resulted in a smaller depolarization ofV B in the UUOOK, but in a greater depolarization in the UUOCK. Upon lowering bath Cl-, the change in basolateral membrane electromotive force (AEMF) was increased in the UUOOK, and decreased in the UUOCK. Reversely, upon raising bath K+, the AEMF was decreased in the UUOOK, and increased in the UUOCK. We conclude: (a) the conductances of Na+ and K+ in the apical membrane, and active Na+-K+ pump activity and relative K+ conductance in the basolateral membrane are decreased in the UUOOK, and increased in the UUOCK; (b) the relative basolateral membrane CI-conductance was increased in the UUOOK, and decreased in the UUOCK. Unilateral ureteral obstruction (UUO)' causes a number of alterations in renal function ofboth obstructed and untouched contralateral kidneys ( 1, 2). Abnormalities in Na+ and water conservation and in H+ and K+ excretion (3-9) are known to occur in the distal nephron segments, including the cortical collecting duct (CCD), from the obstructed kidney after UUO. However, the mechanisms underlying these disorders have not been fully evaluated. Only a few studies have assessed some of them at a segmental level. The in vitro microperfusion studies of the rabbit CCD have demonstrated that ureteral obstruction led to decreases in the lumen-negative transepithelial voltage (6, 8) as well as in Na+ reabsorption (6). These changes also included decreases in Na+-K+-ATPase activity (9) and in Na+-K+ pump in situ turnover (4) in the CCD from the obstructed rat kidney after UUO. These observations have suggested that the collecting duct (CD) cell would be functionally impaired after ureteral obstruction, because the CD cell is mainly responsible for Na+ and K+ transports in the CCD (10-15). However, the cellular mechanisms of the defects in Na+ and K+ transports in the CCD from obstructed kidneys remain unknown.In addition, there is little information regardi...