Hypochlorite-induced porcine model of peritoneal fibrosis through the activation of IL1β-CX3CL1-TGFβ1 signal axis
Journal
Scientific Reports
Journal Volume
10
Journal Issue
1
Pages
11496
Date Issued
2020
Author(s)
Hsu, Y.-T.
Wu, C.-H.
Chao, C.-Y.
Wei, Y.-S.
Chang, Y.-C.
Tsai, S.-Y.
Lee, Y.-J.
Abstract
Patients with kidney failure rely on life-saving peritoneal dialysis to facilitate waste exchange and maintain homeostasis of physical conditions. However, peritoneal dialysis often results in peritoneal fibrosis and organ adhesion that subsequently compromise the efficiency of peritoneal dialysis and normal functions of visceral organs. Despite rodent models provide clues on the pathogenesis of peritoneal fibrosis, no current large animal model which shares high degree of physiological and anatomical similarities to human is available, limiting their applications on the evaluation of pre-clinical therapeutic efficacy. Here we established for the first time, hypochlorite-induced porcine model of peritoneal fibrosis in 5-week-old piglets. We showed that administration 15–30?mM hypochlorite, a dose- and time-dependent severity of peritoneal fibrosis characterized by mesothelium fragmentation, αSMA+ myofibroblasts accumulation, organ surface thickening and type I collagen deposition were observed. We also demonstrated in vitro using human mesothelial cells that hypochlorite-induced fibrosis was likely due to necrosis, but not programmed apoptosis; besides, overexpression of IL1β, CX3CL1 and TGFβ on the peritoneal mesothelium in current model was detected, similar to observations from peritoneal dialysis-induced peritoneal fibrosis in human patients and earlier reported mouse model. Moreover, our novel antemortem evaluation using laparoscopy provided instant feedback on the progression of organ fibrosis/adhesion which allows immediate adjustments on treatment protocols and strategies in alive individuals that can not and never be performed in other animal models. ? 2020, The Author(s).
SDGs
Other Subjects
collagen type 1; fractalkine; hypochlorous acid; interleukin 1beta; transforming growth factor beta1; animal; disease model; epithelium cell; genetics; human; metabolism; myofibroblast; pathology; peritoneal dialysis; peritoneal fibrosis; peritoneum; pig; signal transduction; Animals; Chemokine CX3CL1; Collagen Type I; Disease Models, Animal; Epithelial Cells; Humans; Hypochlorous Acid; Interleukin-1beta; Myofibroblasts; Peritoneal Dialysis; Peritoneal Fibrosis; Peritoneum; Signal Transduction; Swine; Transforming Growth Factor beta1
Publisher
Nature Research
Type
journal article