mart-1-antigen and Fibrosis

Renal fibrosis plays a pivotal role in the development and progression of chronic kidney disease, which affects 10% of the adult population. Previously, it has been demonstrated that the cyclooxygenase-2 (COX-2)/prostaglandin (PG) system influences the progression of renal injury. Here, we evaluated the impact of butaprost, a selective EP. We studied the anti-fibrotic efficacy of butaprost using Madin-Darby Canine Kidney (MDCK) cells, mice that underwent unilateral ureteral obstruction and human precision-cut kidney slices. Fibrogenesis was evaluated on a gene and protein level by qPCR and Western blotting.. Butaprost (50 μM) reduced TGF-β-induced fibronectin (FN) expression, Smad2 phosphorylation and epithelial-mesenchymal transition in MDCK cells. In addition, treatment with 4 mg/kg/day butaprost attenuated the development of fibrosis in mice that underwent unilateral ureteral obstruction surgery, as illustrated by a reduction in the gene and protein expression of α-smooth muscle actin, FN and collagen 1A1. More importantly, a similar anti-fibrotic effect of butaprost was observed in human precision-cut kidney slices exposed to TGF-β. The mechanism of action of butaprost appeared to be a direct effect on TGF-β/Smad signalling, which was independent of the cAMP/PKA pathway.. In conclusion, this study demonstrates that stimulation of the EP

Topics: Aged; Alprostadil; Animals; Cell Line; Dogs; Epithelial-Mesenchymal Transition; Female; Fibrosis; Humans; Kidney; Kidney Diseases; Male; MART-1 Antigen; Mice; Mice, Inbred C57BL; Receptors, Prostaglandin E, EP2 Subtype; Tissue Culture Techniques; Ureteral Obstruction; Urological Agents