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

Blocking TGF-β1 Protects the Peritoneal Membrane from Dialysate-Induced Damage

“…We have previously shown that in response to PD, the pathologic fibroblasts may originate from resident fibroblasts and from the mesothelium via MMT. 11,12,39,46 Herein, we provide evidence for the first time that peritoneal FSP-1 ϩ fibroblasts may also derive from bone-marrow-derived circulating cells (CD45ϩ) and from the local conversion of endothelial cells (CD31ϩ) via EnMT. The percentage of mesothelial-cell-derived FSP-1 ϩ fibroblasts, 37%, in the injured peritoneum is in agreement with that found in renal fibrosis, in which approximately 36% come from local conversion of tubular epithelial cells via epithelialto-mesenchymal transition.…”

“…39,46 In the peritoneum from control saline-treated mice, there was no expression of FSP-1. By contrast, FSP-1 ϩ fibroblasts were present in the submesothelial compact region of mice treated with PD fluid ( Figure 5, A and B).…”

“…These treatments are proven to be good in vitro models of MMT. 11,16,39,46 When indicated, TGF-␤1-blocking peptide P17 was used at a final concentration of 150 g/ml. This dose of P17 was similar to that used in previous studies.…”

“…PD fluid or saline solution were instilled via a peritoneal catheter connected to an implanted subcutaneous mini access port (Access Technologies, Skokie, IL) as described previously. 16,46,50 During the first week after surgery, the animals implanted with a peritoneal access port (n ϭ 44) received 0.2 ml of saline with 1 IU/ml of heparin to facilitate wound healing. Thereafter, during a 5-week period, 8 mice were daily instilled with 1.5 ml of saline solution (control; n ϭ 8), 12 mice were daily instilled with 1.5 ml of standard PD fluid composed of 4.25% glucose and buffered with lactate (Stay Safe, Fresenius, Bad Homburg, Germany) and treated with control peptide (4 mg/kg per day; PDF group), 12 mice were daily instilled with 1.5 ml of standard PD fluid and treated with P17 (4 mg/kg per day; PDFϩP17 group), and 12 mice were daily instilled with 1.5 ml of standard PD fluid and treated with P144 (4 mg/kg per day; PDFϩP144 group).…”

Pharmacologic Targets and Peritoneal Membrane Remodeling

“…In experimental models of both diabetic and nondiabetic chronic kidney disease, they have demonstrated antifibrotic effects (33,34). Oral administration of rosiglitazone to mice treated with PD fluid reduced AGE formation, peritoneal thickness, and angiogenesis; preserved the mesothelium; and resulted in less expression of myofibroblasts and in improved peritoneal function (35). In a small randomized crossover trial of continuous ambulatory PD patients treated with pioglitazone, Li et al (36) found improvement of insulin resistance and reduced levels of C-reactive protein, indicating that pioglitazone might diminish inflammation in PD patients.…”