Inhibiting effect of short hairpin RNA on expression of transforming growth factor-β1 in human peritoneal mesothelial cells induced by peritoneal dialysis solution

摘要

The peritoneum response to peritoneal dialysis can lead to fibrosis. The transforming growth factor-β1 (TGF-β1 ) plays an important role in regulating tissue repair and remodeling after injury. Excessive synthesis and deposition of matrix proteins by peritoneal mesothelial cells can lead to structural and functional changes in the peritoneal membrane, jeopardizing the long-term efficacy of peritoneal dialysis (PD). Prolonged exposure to high glucose concentrations in PD fluid has been implicated as a major stimulus to matrix accumulation, through the induction of transforming growth factor-β1 (TGF-β1). Prolonged exposure of human peritoneal mesothelial cells (HPMC) to high glucose concentrations in peritoneal dialysate is the principal factor leading to matrix accumulation and thickening of the peritoneal membrane, accompanied by progressive deterioration of transport functions. These changes are mediated in part through the induction of transforming growth factor-beta 1 (TGF-β1 ). RNA interference (RNAi) is an evolutionary conserved process, in which the introduction of double-stranded RNA into a cell lead to specific suppression of gene expression. RNAi has become an important tool for gene function studies and may have therapeutic potential. This study aimed at inducing RNAi in human peritoneal mesothelial cells by short hairpin RNAs (shRNA) generated from a DNA vector, thereby, to provide a new approach to preventing and treating peritoneal fibrosis.