Leishmania infantum-chagasi activates SHP-1 and reduces NFAT5/TonEBP activity in the mouse kidney inner medulla.

Leishmania infantum-chagasi activates SHP-1 and reduces NFAT5/TonEBP activity in the mouse kidney inner medulla.
Am J Physiol Renal Physiol. 2014 Jul 2;
Authors: Zhou X, Wang H, Koles NL, Zhang A, Aronson NE
Abstract
Visceral leishmaniasis patients have been reported to have a urine concentration defect. Concentration of urine by the renal inner medulla is essentially dependent on a transcription factor, NFAT5/TonEBP, because it activates expression of osmoprotective genes BGT1 and SMIT, and water channel aquaporin-2, all of which are imperative for concentrating urine. Leishmania parasites evade macrophage immune defenses by activating protein tyrosine phosphatases, among which SHP-1 is critical. We previously demonstrated that SHP-1 inhibits tonicity-dependent activation of NFAT5/TonEBP in HEK293 cells through screening a genome-wide siRNA library against phosphatases. We sought to examine whether Leishmania can activate SHP-1 and inhibit NFAT5/TonEBP activity in the renal inner medulla in a murine model of Visceral leishmaniasis by injection of female BALB/c mice with a single intravenous dose of 5X105 L. chagasi metacyclic promastigotes. We found that SHP-1 is expressed in the kidney inner medulla. L. chagasi activates SHP-1 with an increase of stimulatory phosphorylation of SHP-1-Y536 in the region. L. chagasi reduces expression of NFAT5/TonEBP mRNA and protein as well as expression of its targeted genes: BGT1, SMIT and aquapori...

Source: Am J Physiol Renal P... - July 2, 2014 Category: Urology & Nephrology Authors: Zhou X, Wang H, Koles NL, Zhang A, Aronson NE Tags: Am J Physiol Renal Physiol Source Type: research