SELECTIVE RESPONSE OF IRON CYCLE PROTEINS THROUGH IRON AND ERYTHROPOIETIN SIGNALS IN MOUSE KIDNEY.

FERNANDEZ DELIAS MARIA FLORENCIA; ROQUE MARTA ELENA

Congreso; reunion anual de las sociedades de biociencia; 2020

SAIC

Iron overload can be regulated by different mechanisms related to erythropoiesis and kidney tissue.Taking into account the labile nature of iron,its circulation and storage are strictly controlled.Approaches to addressing iron trafficking through the hepcidin regulator and importer(DMT1,ZIP14) and exporter(FPN) proteins may offer new insights.The presence of the erythropoietin receptor(EPO-R)in the kidney suggests various non-erythropoietic functions of EPO.This study was designed to extend our previous studies on the relationship between iron overload and iron protein regulation to another important organ,the kidney.The non-erythropoietic functions of EPO will also be analysed.CF1mice(25±5g;3m)split in(n=4/group):1)Iron-adequate(IA);2)Iron-overload(IO)(ironsaccharate;days0,4,8,12ip;1800mg/kg);3)EPO(days17-19ip;20000UI/kg);4)Iron-overload+EPO(IO+EPO).Immunohistochemistry:anti-DMT1(divalent-metal-transporter1),anti-ZIP14(Zrt-Irt-likeProtein14),anti-prohepcidin.Iron levels Wiener kit.The Protocol was approved by CICUAE-UNS.Iron levels showed an increase in IO/IO+EPO respect to IA/EPO.Abundant hemosiderin was observed in IO in the proximal tubule S2(PTS2),glomerulus and medulla;it was moderate in IO+EPO and scarce in EPO/IA.The DMT1 expression was evident in the PTS2 and medulla in IA/EPO and slight in IO/IO+EPO.In IO the ZIP14 expression was intense in PTS2 and medulla and slight in EPO being this the predominant signal.The prohepcidin expression was intense in IO/IO+EPO and slight in IA/EPO.We can conclude that in iron overload,a coordinated regulation of the iron cycle proteins occurs in the kidney,suggesting a protective mechanism against iron excess due to the reduction of iron uptake according to the following modifications:decrease in both the uptake of DMT1 and the release of FPN,also showing a negative regulation of kidney-DMT1 by hepcidin.The cytoprotective role of EPO in controlling iron storage could be explained by the reduced expression of ZIP14 observed.