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Mice with an absent stress response are protected against ischemic renal injury.

Kidney international (2014-05-09)
Rajasree Sreedharan, Shaoying Chen, Melody Miller, Dipica Haribhai, Calvin B Williams, Scott K Van Why
ABSTRACT

Inducible heat shock proteins (HSPs), regulated by heat shock factor-1 (HSF-1), protect against renal cell injury in vitro. To determine whether HSPs ameliorate ischemic renal injury in vivo, HSF-1 functional knockout mice (HSF-KO) were compared with wild-type mice following bilateral ischemic renal injury. Following injury, the kidneys of wild-type mice had the expected induction of HSP70 and HSP25; a response absent in the kidneys of HSF-KO mice. Baseline serum creatinine was equivalent between strains. Serum creatinine at 24 h reflow in HSF-KO mice was significantly lower than that in the wild type. Histology showed similar tubule injury in both strains after ischemic renal injury but increased medullary vascular congestion in wild-type compared with HSF-KO mice. Flow cytometry of mononuclear cells isolated from kidneys showed no difference between strains in the number of CD4(+) and CD8(+) T cells in sham-operated animals. At 1 h of reflow, CD4(+) and CD8(+) cells were doubled in the kidneys of wild-type but not HSF-KO mice. Foxp3(+) T-regulatory cells were significantly more abundant in the kidneys of sham-operated HSF-KO than wild-type mice. Suppression of CD25(+)Foxp3(+) cells in HSF-KO kidneys with the anti-CD25 antibody PC61 reversed the protection against ischemic renal injury. Thus, HSF-KO mice are protected from ischemic renal injury by a mechanism that depends on an increase in the T-regulatory cells in the kidney associated with altered T-cell infiltration early in reflow. Hence, stress response activation may contribute to early injury by facilitating T-cell infiltration into ischemic kidney.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Percoll®, pH 8.5-9.5 (20 °C)
Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-15, ascites fluid