Effects of glucose dialysate on extracellular matrix production by human peritoneal mesothelial cells (HPMC): the role of TGF‐β

Abstract

These data suggest that the pro-fibrotic effect of glucose dialysate on HPMC is mediated through stimulation of TGF-beta, which promotes FN gene expression and protein production.

Short-term peaks in glucose promote renal fibrogenesis independently of total glucose exposure

“…Prior studies demonstrated a profibrotic effect in fibroblasts following exposure to glucose concentrations of greater than 25 mM glucose (18). Clearly, the clinical relevance of these experiments is likely to be minimal as most patients do not have prolonged periods with blood glucose levels that are persistently at this level.…”

TGF-β1 Gene Polymorphisms and Peritoneal Equilibration Test Results in CAPD Patients

“…[8,22] It might be that the increased TGF-βl expression by MCs induced by high glucose or inflammatory state play an important role in peritoneal fibrosis and loss of function as an ultrafiltration barrier in chronic PD patients. [4,11] There are two important limitations in this study: a lack of the peritoneal biopsy that evaluated peritoneal fibrosis, and a lack of the results of plasma TGF-β1 levels.…”

“…There are several in vivo and in vitro studies supporting this hypothesis. [1,4,10,11] TGF-βl decreases both extracellular matrix accumulation and degradation and increases type 1-3 collagen synthesis. The reasons for high production of TGF-βl in peritoneum are still unclear in peritoneal dialysis patients.…”

“…A high glucose environment is known to stimulate TGF-βl expression in various cell types. [4,5,11] TGF-β1 expression by MCs exposed to a high glucose milieu (15-45 times higher than normal) in vitro has been studied to evaluate the role of high glucoseinduced TGF-β1 synthesis in the development of peritoneal fibrosis. [14] Kumano et al reported that a high glucose content increased the TGF-β1 gene expression of rat MCs in association with decreased MC proliferation and regeneration.…”

“…[4,5,11] TGF-β1 expression by MCs exposed to a high glucose milieu (15-45 times higher than normal) in vitro has been studied to evaluate the role of high glucoseinduced TGF-β1 synthesis in the development of peritoneal fibrosis. [14] Kumano et al reported that a high glucose content increased the TGF-β1 gene expression of rat MCs in association with decreased MC proliferation and regeneration. [15] They suggested that TGF-β1 played a central role in mediating the biological effect of high glucose dialysate on peritoneal MCs, leading to peritoneal fibrosis.…”