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Increased Susceptibility of Aging Kidney to Ischemic Injury: Role of Aberrant MMP‐7 Expression
Author(s) -
Chen Gang,
Bridenbaugh Eric,
Zawieja Dave,
parrish alan
Publication year - 2006
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.20.4.a341-c
Subject(s) - kidney , gene expression , caloric theory , microarray analysis techniques , microarray , senescence , analysis of variance , biology , ischemia , gene , intracellular , medicine , acute kidney injury , endocrinology , genetics
Aging is associated with an increased incidence and severity of acute renal failure; however, the molecular mechanisms underlying the increased susceptibility remain undefined. These experiments were designed to investigate the influence of age on the response of the kidney to ischemia. Renal slices were prepared from young (5 month), aged ad libitum (24 month) and aged caloric restricted (24 month) male Fischer 344 rats and subjected to ischemic stress (anoxia, 100% N2) for 0–60 min or to the nephrotoxicant cisplatin (2 mM, 4 hr). As assessed by intracellular ATP and GSH content, and LDH and alpha‐GST leakage into the culture media, slices from aged ad libitum rats were more susceptible to injury than young counterparts. Importantly, caloric restriction attenuated this increased susceptibility to injury. In an attempt to identify molecular pathway(s) underlying this response, microarray analysis was performed on tissue harvested from the same animals used for the functional analysis. RNA was isolated and the corresponding cDNA was hybridized to CodeLink™ Rat Whole Genome Bioarray slides. Subsequent gene expression analysis was performed using GeneSpring software. Using a 2‐fold difference as a cut‐off and a Welch ANOVA (Benjamini and Hochberg False Discovery Rate of 0.05), we identified 131 genes whose pattern of expression suggested that caloric restriction attenuated a change induced by aging. The expression of 42 genes was reduced during aging but rescued by caloric restriction. The expression of 89 genes was increased during aging but attenuated by caloric restriction, including MMP‐7. In summary, we have identified several changes in gene expression that may be associated with the increased susceptibility of aging kidney to ischemic insult.