Korean Journal of Nephrology 1999;18(3):353-364.

인간 복막 중피 세포의 Transforming Growth Factor-β1(TGF-β1) 합성에 관한 연구 (Transforming Growth Factor-β1(TGF-β1) Synthesis of Human Peritoneal Mesothelial Cell)

윤견일, 강덕희, 임현정, 홍영숙, 최진희, 한대석 (Kyun Il Yoon, Duk Hee Kang, Hyun Joung Lim, Young Suk Hong, Jin Hee Choi and Dae Suk Han)

Abstract

Objective:to investigate the effect of high glucose and spent peritoneal dialysate on the TGF-β1 synthesis of cultured human peritoneal MC(HPMC); to examine the effect of costimulation with high glucose or dialysate and cytokines, interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α), on transforming growth factor(TGF-β1) synthesis of HPMC. Design:HPMCs were exposed to different concentrations of glucose(30, 60 & 90 mM/L) or spent peritoneal dialysate for 48 hours in the absence or presence of IL-1β(1ng/ml) and TNF-α(1ng/ml). TGF-β1 mRNA expression was assessed by Northern blot analysis and TGF-β1 protein synthesis and release by Western blot analysis with immunoprecipitation.
Results
Exposure of MC to high glucose condition(30mM, 60mM & 90mM of D- glucose) induced 2.3-, 3.6- and 4.0-fold increases in TGF-β1 mRNA expression of MC with enhanced TGF-β1 protein synthesis and secretion into the media. Incubation with spent dialysate also significantly increased TGF-β1 mRNA expression & protein secretion compared to control media(P<0.05) Stimulation with IL-1β(1ng/ml) or TNF-α(1ng/ml) significantly increased TGF-β1 mRNA expression after 48 hours above the control level by 2.7-fold and 2.1-fold, respectively. However, TNF-α-induced increase in TGF-β1 mRNA expression was not translated into TGF-β1 protein secretion whereas IL-1β stimulation induced a significant increase in TGF-β1 protein secretion as well as TGF-β1 mRNA expression. Combined stimulation of high glucose or spent dialysate together with IL-1β or TNF-α showed a greater increase in TGF-β1 mRNA expression and protein secretion compared to stimulation with high glucose or spent dialysate alone.
Conclusion
Our results clearly show that high glucose concentration of peritoneal dialysate and spent dialysate themselves might be sufficient to stimulate the production of TGF-β1 by peritoneal mesothelial cell. This state of chronic induction of TGF-β1 is further exaggerated in the presence of peritonitis because of stimulatory effect of proinflammatory cytokines, resulting in the augmented TGF-β1 synthesis, thus promoting peritoneal fibrosis.