Renal endothelial protein C receptor expression and shedding during diabetic nephropathy

摘要: UNLABELLED Essentials Endothelial protein C receptor (EPCR) promotes diabetic nephropathy (DN) outcome improvement. Renal expression and shedding of EPCR were measured in patients with or without DN. Inhibition metalloproteinase-driven restored glomerular endothelium phenotype. through metalloproteinase ADAM17 contributes to the worsening SUMMARY Background Diabetic represents leading cause end-stage renal disease. The endothelial its ligand (activated C) have been shown ameliorate phenotype DN mice. activity can be regulated by proteolytic cleavage involving ADAMs, yielding a soluble form (sEPCR). Objective To characterize during Methods levels plasma, urine biopsy samples (n = 73) 63) ADAM-induced was investigated vitro human cell line. Results showed higher plasma urinary sEPCR than controls (112.2 versus 135.2 ng mL(-1) 94.35 140.6 , respectively). Accordingly, markedly reduced DN, this associated increased ADAM-17 ADAM-10. In vitro, induced incubation high-glucose medium, suppressed inhibition silencing, which led improved vascular cadherin (VE-cadherin) mRNA transforming growth factor (TGF)-β. addition, silencing minor effects on VE-cadherin but significant increase TGF-β expression. Conclusion ADAM-driven endothelium, whereas enhanced TGF-β, marker endothelial-mesenchymal transition. These findings demonstrate that driven ADAMs