MICROVESCICOLE (MV) ORIGINATE DA CELLULE PROGENITRICI ENDOTELIALI (EPC) PROTEGGONO I RENI DAL DANNO DA ISCHEMIA-RIPERFUSIONE (IRI) MEDIANTE RIPROGRAMMAZIONE DELLE CELLULE (CELL) RENALI RESIDENTI DIPENDENTE DA MICRORNA (miRNA)

[Machine translation] introduction. EPC are circulating bone marrow cells that promote cell regeneration with paracrine mechanisms such as secretion of growth factors or other cellular products including MVs, membrane particles essential in communication between cells. MVs released by EPC activate angiogenesis in endothelial cells through RNA transfer. , purpose. 1) EPC-derived MVs can prevent acute kidney injury (AKI) linked to IRI; 2) Identification of miRNAs transferred from MVs in the reprogramming of hypoxic renal resident cells., Materials and Methods. MVs were isolated from EPC by ultracentrifugation supernatants and characterized by proteins and RNA. IRI induced in rats by vascular clamping for 45 min. Isolation from human kidney of endothelial cells, epithelium , tubular and CD133+ progenitors. Exposed these cells to hypoxia to recreate IRIS. Also use MVs pretreated with 1 U/ml of RNase or MVs from EPCs deprived of miRNA via Dicer knock-down (siRNA). , Results. MVs are located in peritubular capillaries and tubules, providing protection from AKI, reducing apoptosis, stimulating angiogenesis and tubular cell proliferation and inhibiting leukocyte infiltration. In vitro, MVs inhibit hypoxial apoptosis and endothelial and tubular functional alterations; they also stimulate genes involved in proliferation, angiogenesis and apoptosis inhibition. MV , they also induce differentiation of CD133+ progenitors in endothelium. The protective effect of MV is reduced if pretreated with RNase or Dicer siRNA., Conclusions. EPC-derived MVs protect against IRI-linked AKI by reprogramming resident hypoxic kidney cells mediated by miRNA transfer