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Mice with an absent stress response are protected against ischemic renal injury. Kidney Int 2014 Sep;86(3):515-24

Date

05/09/2014

Pubmed ID

24805105

Pubmed Central ID

PMC4149847

DOI

10.1038/ki.2014.73

Scopus ID

2-s2.0-84907598808   7 Citations

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.

Author List

Sreedharan R, Chen S, Miller M, Haribhai D, Williams CB, Van Why SK

Authors

Scott K. Van Why MD Professor in the Pediatrics department at Medical College of Wisconsin
Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acute Kidney Injury
Animals
Antibodies, Monoclonal
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Creatinine
DNA-Binding Proteins
Forkhead Transcription Factors
HSP70 Heat-Shock Proteins
Heat Shock Transcription Factors
Heat-Shock Proteins
Interleukin-2 Receptor alpha Subunit
Kidney Tubules
Male
Mice
Mice, Knockout
Molecular Chaperones
Neoplasm Proteins
Reperfusion Injury
Stress, Physiological
T-Lymphocytes, Regulatory
Transcription Factors