Epithelial to Mesenchymal Transition and Peritoneal Membrane Failure in Peritoneal Dialysis Patients

GSK-3β inhibition protects mesothelial cells during experimental peritoneal dialysis through upregulation of the heat shock response

“…Although several of the previously studied stressors relevant for GSK-3β activation, such as changes in glucose concentrations and high GDP content, are also known to be major factors of PDF toxicity (Aroeira et al 2007) (Hooper 2007), to our knowledge, there are no data yet on GSK-3β in PD. As a first step, we therefore investigated the activation and expression of GSK-3β in mesothelial cells in an in vitro PD model, established recently by our group in order to study the cellular stress responses upon exposure to PDF (Kratochwill et al 2012).…”

PPAR-γ agonist rosiglitazone protects peritoneal membrane from dialysis fluid-induced damage

“…1,2 The morphology of the peritoneal membrane is simple as it is comprised of a single layer of mesothelial cells that covers a submesothelial region composed of connective tissue containing a few fibroblasts, mast cells, macrophages, and vessels. 3 Mesothelial cells are the key regulators of peritoneal homeostasis, and they participate in peritoneal immune and inflammatory responses, providing protection against invading microbes. 3,4 Chronic exposure to non-physiological PD solutions and episodes of infection cause inflammation and damage to the peritoneal membrane, which undergoes a loss of the mesothelial cells monolayer, submesothelial fibrosis, angiogenesis and hyalinizing vasculopathy.…”

“…3 Mesothelial cells are the key regulators of peritoneal homeostasis, and they participate in peritoneal immune and inflammatory responses, providing protection against invading microbes. 3,4 Chronic exposure to non-physiological PD solutions and episodes of infection cause inflammation and damage to the peritoneal membrane, which undergoes a loss of the mesothelial cells monolayer, submesothelial fibrosis, angiogenesis and hyalinizing vasculopathy. [5][6][7] These morphological alterations are associated with increased rates of small-solute transport and with ultrafiltration dysfunction of the peritoneal membrane.…”

“…[5][6][7] These morphological alterations are associated with increased rates of small-solute transport and with ultrafiltration dysfunction of the peritoneal membrane. 3,5,8 The patho-physiological mechanisms underlying the peritoneal structural and functional impairment are still not fully clear. Inflammatory cells and myofibroblasts are considered to be mainly responsible for peritoneal membrane deterioration during long-term PD.…”

Endoplasmic reticulum stress as a novel target to ameliorate epithelial-to-mesenchymal transition and apoptosis of human peritoneal mesothelial cells

“…8,9 EMT in PD patients was associated with ultrafiltration failure, which highlighted the clinical significance of peritoneal EMT as a cause of peritoneal dysfunction. 5,6,41 ER stress has been implicated in EMT and fibroblast accumulation in organ fibrosis. 42 One of the chemical inducers of ER stress, TM, was reported to induce EMT of renal proximal tubular cells via the release of calcium from the ER and the activation of Wnt signaling.…”