장기간 복막투석시 발생하는 섬유화에 대한 TGF-β1 Antisense의 억제 효과

Abstract

Ultrafiltration failure is a major cause of dropout of long-term peritoneal dialysis (PD), and often related to peritoneal fibrosis. High glucose solution in dialysate has been implicated as a culprit of peritoneal fibrosis in long-term PD patients. We examined the protective effect of TGF-β1 antisense on peritoneal fibrosis. Human peritoneal mesothelial cells (HPMCs) were isolated from omentum and divided into three groups as control, incubated with high glucose, and incubated with high glucose and transfected TGF-β1 antisense groups. In animal experiment, Spraue-Dawley rats were divided into two groups as control PD group and TGF-β1 antisense treated PD groups. The degree of fibrosis were assayed by RT-PCR, H&E stain, immunohistochemistry stain and Masson’s Trichrome stain. The TGF-β1 expression in vitro increased 1.6 times in the group treated with high glucose solution, and was normalized by the addition of TGF-β1 antisense. In the animal model of PD, submesothelial thickening and depositions of collagen were seen under light microscopy. The degree of peritoneal fibrosis increased with the time on PD treatment. The addition of TGF-β1 antisense into the dialysate reduced the deposition of collagen, however, it failed to show the protective effect against peritoneal thickening. In conclusion, the present study demonstrates that high glucose up-regulates TGF-β1 expression in the cultured HPMCs, which is normalized by addition of TGF-β1 antisense. The protective effect of TGF-β1 antisense on peritoneal fibrosis could not be demonstrated in the animal model of PD.