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Peritoneal fibrosis induced by intraperitoneal methylglyoxal injection: the role of concurrent renal dysfunction
Akira Onishi1, Tetsu Akimoto, Yoshiyuki Morishita
1Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan.
Background:
Peritoneal fibrosis (PF) is a serious pathophysiology of peritoneal dialysis (PD). An ongoing focus of research is the potential fibrogenic nature of methylglyoxal (MGO) in conventional PD fluid (PDF). The aim of the current study was to explore the effects of the uremic milieu on the promotion of PF by MGO using rats with adenine-induced renal failure (RF).
Methods:
Adenine-treated Sprague-Dawley rats were randomly assigned to receive continuous peritoneal injections of PDF with or without MGO for three weeks or were left untreated for the same duration. Rats without RF were also assigned to three groups. The peritoneal histology and expression levels of type I collagen, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (αSMA), Snail, matrix metalloproteinase-2 (MMP-2), advanced glycation end-products (AGEs) and the receptor for AGE (RAGE) were then analyzed.
Results:
Peritoneal treatment with 5 mM MGO accelerated the fibrous peritoneal thickening progression promoted by exposure to standard PDF in the rats with RF, but not in the rats with a normal renal function. Treatment with MGO significantly augmented the proliferation of mesenchymal-like mesothelial cells, accumulation of AGE, de novo expression of αSMA and RAGE and gene expression of type I collagen, TGF-β1, Snail and MMP-2, whereas both MGO and RF alone had, at most, marginal effects on the changes in these biological parameters.
Conclusions:
In the present study, the adverse effects of MGO on the peritoneum became more prominent under conditions of a uremic milieu. These findings imply that MGO and uremia act cooperatively to induce PF.
Insights
Methylglyoxal (MGO) in peritoneal dialysis fluid exacerbates peritoneal fibrosis (PF) in rats with kidney failure. Uremia amplifies MGO’s fibrotic effects, suggesting a cooperative role in promoting PF.
Area of Science:
- Nephrology
- Pathophysiology
- Biochemistry
Background:
- Peritoneal fibrosis (PF) is a significant complication of peritoneal dialysis (PD).
- Methylglyoxal (MGO), a component of conventional PD fluid (PDF), is investigated for its fibrogenic potential.
- The study examines how a uremic environment influences MGO's role in promoting PF.
Purpose of the Study:
- To investigate the synergistic effects of methylglyoxal (MGO) and a uremic milieu on the development of peritoneal fibrosis (PF).
- To evaluate the impact of MGO exposure in the context of adenine-induced renal failure (RF) in a rat model.
Main Methods:
- Rats with adenine-induced renal failure (RF) and healthy controls received peritoneal injections of PDF with or without MGO.
- Peritoneal histology was analyzed.
- Expression levels of key fibrotic markers including collagen type I, TGF-β1, αSMA, Snail, MMP-2, AGEs, and RAGE were assessed.
Main Results:
- MGO significantly accelerated peritoneal thickening in rats with RF exposed to PDF, but not in healthy rats.
- MGO treatment increased mesenchymal-like mesothelial cell proliferation, AGE accumulation, and expression of αSMA, RAGE, collagen type I, TGF-β1, Snail, and MMP-2.
- Both MGO and RF alone had minimal impact on these parameters.
Conclusions:
- The pro-fibrotic effects of MGO on the peritoneum are significantly enhanced under uremic conditions.
- MGO and uremia act cooperatively to induce peritoneal fibrosis (PF).
