Project title
Lysyl Oxidase 在腹膜纖維化的角色
Internal ID
NSC102-2314-B002-023-MY3
Principal Investigator
Start Date
August 1, 2014
End Date
July 12, 2015
Investigators
Organizations
Partner Organizations
Project Web Site
The Role of Lysyl Oxidase in Peritoneal Fibrosis = Lysyl Oxidase 在腹膜纖維化的角色
Keywords
離胺基酸氧化腺
腹膜透析
葡萄糖
腹膜纖維化
細胞激素
lysyl oxidase
peritoneal dialysis
glucose
peritoneal fibrosis
cytokine
Description
Chronic dialysis is a life-sustaining treatment for patients with end stage renal disease. However, long-term PD is limited because of structural and functional alternation of the peritoneal membrane. The unique pathological finding is thickened submesothelial zone, which composed with dense collagen deposition. The peritoneal fibrosis would lead to ultrafiltration failure, technique failure, and even catastrophic encapsulating peritoneal sclerosis. The main and common final presentation of peritoneal fibrosis is an inappropriate accumulation of matrix within peritoneal tissue. We propose extracellular matrix cross-link is critical to its excess deposit and contributes to peritoneal fibrosis. Lysyl oxidase (LOX) is a copper- and lysyl-tyrosyl cofactor containing amine oxidase that has been known to play a critical role in the catalysis of crosslinks in extracellular matrix proteins.In various tissue and cells, lysyl oxidase is upregulated by hypoxia status, high glucose and cytokines, including transforming growth factorp , platelet-derived growth factor, and fibroblast growth factor. However, the effect of LOX in peritoneal fibrosis has not been delineated. Since unphysiological dialysate, often with high glucose, is used in peritoneal dialysis, and is associated with many growth factors and inflammatory cytokines and PF, we hypothesize LOX is upregulated in the peritoneal fluid due to high glucose dialysate or inflammatory cytokines and then leads to extracellular matrix cross-link and promotes peritoneal fibrosis. In the present study, we aim to explore the role of lysyl oxidase in peritoneal function and fibrosis. We plan to explore the molecular mechanism of regulation of lysyl oxidase in human primary mesothelial cells and peritoneal fibroblasts. Then, we aim at designing an in vitro peritoneal equivalent via organotypic cultures and examine whether high glucose-induced changes in LOX activity may contribute to surplus permeability.