%0 Journal Article
%T Hypoxia, cytokines and stromal recruitment: parallels between pathophysiology of encapsulating peritoneal sclerosis, endometriosis and peritoneal metastasis
%A Robert Beaumont Wilson
%J Archive of "Pleura and Peritoneum".
%D 2018
%R 10.1515/pp-2018-0103
%X Peritoneal response to various kinds of injury involves loss of peritoneal mesothelial cells (PMC), danger signalling, epithelial-mesenchymal transition and mesothelial-mesenchymal transition (MMT). Encapsulating peritoneal sclerosis (EPS), endometriosis (EM) and peritoneal metastasis (PM) are all characterized by hypoxia and formation of a vascularized connective tissue stroma mediated by vascular endothelial growth factor (VEGF). Transforming growth factor-¦Â1 (TGF-¦Â1) is constitutively expressed by the PMC and plays a major role in the maintenance of a transformed, inflammatory micro-environment in PM, but also in EPS and EM. Persistently high levels of TGF-¦Â1 or stimulation by inflammatory cytokines (interleukin-6 (IL-6)) induce peritoneal MMT, adhesion formation and fibrosis. TGF-¦Â1 enhances hypoxia inducible factor-1¦Á expression, which drives cell growth, extracellular matrix production and cell migration. Disruption of the peritoneal glycocalyx and exposure of the basement membrane release low molecular weight hyaluronan, which initiates a cascade of pro-inflammatory mediators, including peritoneal cytokines (TNF-¦Á, IL-1, IL-6, prostaglandins), growth factors (TGF-¦Á, TGF-¦Â, platelet-derived growth factor, VEGF, epidermal growth factor) and the fibrin/coagulation cascade (thrombin, Tissue factor, plasminogen activator inhibitor [PAI]-1/2). Chronic inflammation and cellular transformation are mediated by damage-associated molecular patterns, pattern recognition receptors, AGE-RAGE, extracellular lactate, pro-inflammatory cytokines, reactive oxygen species, increased glycolysis, metabolomic reprogramming and cancer-associated fibroblasts. The pathogenesis of EPS, EM and PM shows similarities to the cellular transformation and stromal recruitment of wound healing
%K CAPD
%K DAMPs
%K endometriosis
%K EPS
%K HIF
%K hyaluronan
%K peritoneal metastasis
%K TGF-¦Â1
%K VEGF
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405013/