STAT1 regulates macrophage number and phenotype and prevents renal fibrosis after ischemia/reperfusion injury.

STAT1 regulates macrophage number and phenotype and prevents renal fibrosis after ischemia/reperfusion injury. Am J Physiol Renal Physiol. 2018 Nov 07;: Authors: Kemmner S, Bachmann Q, Steiger S, Lorenz G, Honarpisheh M, Foresto-Neto O, Wang S, Carbajo-Lozoya J, Alt V, Schulte C, Chmielewski S, Bluyssen HAR, Heemann U, Baumann M, Lech M, Schmaderer C Abstract Renal ischemia/reperfusion injury (IRI) leads to acute kidney injury or delayed allograft function which predisposes to fibrosis in the native kidney or kidney transplant. Here we investigated the role of the signal transducer and activator of transcription 1 (STAT1) in inflammatory responses following renal IRI. Our study showed that a subsequent stimulation of Janus Kinase 2/STAT1 and toll-like receptor 4 pathways led to greater STAT1 activation followed by increased cytokine transcription compared to single-pathway stimulation in murine renal tubular cells. Moreover, we observed increased activation of STAT1 under hypoxic conditions. In vivo, STAT1-/- mice displayed less acute tubular necrosis and decreased macrophage infiltration 24 hours upon renal ischemia. However, investigation of the healing phase (30 days upon IRI) revealed significantly more fibrosis in STAT1-/- than in wildtype kidneys. In addition, we demonstrated increased macrophage infiltration in STAT1-/- kidneys. Flow cytometry analysis revealed that STAT1 deficiency drives an alternatively activated macrophage...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research