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Role of Age‐Dependent Changes in MMP Expression in Acute Kidney Injury
Author(s) -
Akintola Adebayo D.,
Chen Gang,
Catania Jeffrey M.,
Burghardt Robert C.,
Parrish Alan R.
Publication year - 2008
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.22.1_supplement.942.4
Subject(s) - matrix metalloproteinase , kidney , gelatinase a , medicine , gelatinase , acute kidney injury , endocrinology , collagenase , endogeny , gene expression , biology , enzyme , gene , biochemistry
Aging is associated with an increased incidence and severity of acute renal failure. However, the molecular mechanism(s) underlying the increased susceptibility to injury remain undefined. Given the emerging role of MMPs in ischemic renal injury, the renal mRNA expression of MMPs and their endogenous inhibitors, TIMPs (tissue inhibitor of metalloproteinases), were also examined in young, aged‐AL and aged‐CR rats. Interestingly, age‐dependent increases in the expression of MMP‐7, ‐9, ‐13, and ‐14 were seen, and these changes were attenuated by caloric restriction. The expression of TIMP‐1, but not TIMP‐2 or ‐3, was increased by age and attenuated by caloric restriction. Changes in MMP expression gene expression were paralleled by an age‐dependent increase in collagenase, gelatinase, and membrane type‐MMP activity. Specific increases in MMP‐7, ‐9, and ‐13 activity was seen in urine and kidney tissue, respectively. These results suggest an association between the age‐related increase in susceptibility to injury and overexpression of select MMPs (‐7, ‐9, ‐13, and ‐14) in the kidney, implying a therapeutic potential for inhibition of these MMPs in acute kidney injury.