1. The MEK inhibitor CI‐1040 reverses thickening, fibrosis, and angiogenesis in the parietal peritoneum of Cav1−/− mice upon exposure to PD fluidWT or Cav1−/− mice were exposed to peritoneal dialysis (PD) fluid or sham 5 times per week for three weeks with contemporaneous treatment with CI‐1040 (200 mg/kg) or vehicle.
The MEK inhibitor CI‐1040 reverses thickening, fibrosis, and angiogenesis in the parietal peritoneum of Cav1−/− mice upon exposure to PD fluidWT or Cav1−/− mice were exposed to peritoneal dialysis (PD) fluid or sham 5 times per week for three weeks with contemporaneous treatment with CI‐1040 (200 mg/kg) or vehicle. Eight mice were analyzed per group. Representative hematoxylin and eosin staining of parietal peritoneum sections. Scale bar: 50 μm. Quantification of peritoneal membrane thickness. *P = 0.035 for WT versus Cav1−/− exposed to peritoneal dialysis fluid; *P = 0.04 for Cav1−/− exposed to pertoneal dialysis fluid versus Cav1−/− exposed to peritoneal dialysis fluid and treated with CI‐1040. Representative IF of parietal peritoneal sections stained for pan‐cytokeratin (green) and FSP‐1 (red), and with DAPI to visualize cell nuclei. Scale bar: 30 μm. P = 0.03; P = 0.01. Arrow shows cytokeratin‐FSP‐1 double‐positive MCs invading the submesothelial stroma. Quantification of parietal peritoneal EMT as the number of double‐positive pancytokeratin‐ and FSP‐1‐stained cells. Quantification of CD31‐positive cells; *P = 0.038; **P =  Results of a 30‐min peritoneum equilibration test performed on the last day of the experiment (see Materials and Methods) to measure total peritoneal volumes. **P =  for WT versus Cav1−/− exposed to peritoneal dialysis fluid; **P =  for Cav1−/− exposed to peritoneal dialysis fluid versus Cav1−/− exposed to peritoneal dialysis fluid and treated with CI‐1040.
Raffaele Strippoli et al. EMBO Mol Med. 2014;emmm
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