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The Impact of High Mobility Group Box 1 Protein (HMGB1) on Renal Ischemia‐Reperfusion Injury in Male and Female Spontaneously Hypertensive Rats (SHR)
Author(s) -
Crislip G. Ryan,
Tipton Ashlee J.,
Sullivan Jennifer C.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1114.7
Subject(s) - hmgb1 , medicine , kidney , inflammation , endocrinology , ischemia , immune system , renal cortex , reperfusion injury , immunology
HMGB1 is an endogenous molecule released by dying cells which contributes to renal ischemia‐reperfusion injury (IRI). We recently published that male SHR have more pro‐inflammatory immune cells in the kidney. The goal of this study was to test the hypothesis that female SHR have less HMGB1 than males resulting in a lower degree of renal IRI. HMGB1 levels were measured via ELISA in kidneys of 12 week old male and female SHR (N=5). Additional age matched rats were pre‐treated with control or HMGB1 neutralizing antibody (300 μg/rat via IP; N=4) 1 hour before occluding renal arteries for 1 hour. Renal blood flow velocity (RBV) was measured via ultrasound before and 24 hours after reperfusion. Kidneys were isolated for mRNA extraction and histology. HMGB1 levels were greater in the renal cortex of female vs. male SHR (0.33±0.05 vs. 0.16±0.02 ng/mg; p=0.01). Medullary HMGB1 levels were comparable between sexes. Pre‐treatment with anti‐HMGB1 did not alter RBV compared to controls (% decrease of male SHR: 34±2 to 35±5, NS; female SHR: 35±6 to 22±6, NS) or expression of renal VCAM1 or ICAM1 in either sex. Using histological analysis we determined that anti‐HMGB1 decreased CD3 + T cell infiltration in both sexes, verifying a role for HMGB1 in inflammation following IRI. In conclusion, despite greater renal HMGB1 levels in female SHR, there were no sex differences in the functional role of HMGB1 inhibition on renal IRI or inflammation.