title: Loss of matrix metalloproteinase-8 is associated with worsened recovery after ischemic kidney injury.
abstract: Acute kidney injury (AKI) leads to chronic kidney disease. The mechanisms involved with recovery from AKI are poorly understood and molecular mediators responsible for healing and restoration of kidney function are understudied. We previously discovered differential expression of matrix metalloproteinase-8 (MMP-8) mRNA and protein in patients with severe sepsis associated AKI versus sepsis without AKI. Here, we demonstrate the involvement of MMP-8 in purely ischemic AKI. Mice subjected to 30 min of bilateral renal ischemia developed increased plasma creatinine and MMP-8 expression within 24 h versus sham controls. After an initial surge and subsequent return toward baseline, both kidney MMP-8 expression and activity exhibited a late increase (Days 5-7 post-ischemia reperfusion) in mice subjected to AKI. Neutrophil infiltration of the kidney was significantly higher after AKI in wild-type mice than in MMP-8 null mice, starting at 4 days. Additionally, MMP-8 null mice subjected to AKI demonstrated a persistent histopathologic and functional injury and worsened health (greater overall weight loss) versus wild-type cohorts after seven days. Taken together, our findings suggest that MMP-8 is involved with restoration of baseline kidney health after ischemic kidney injury and that a potential mechanism involves the interaction of MMP-8 and neutrophil recruitment to the site of injury.
authors.affiliation: Division of Critical Care and.
authors.forename: Rajit K
authors.initials: RK
authors.lastname: Basu
authors.forename: Emily
authors.initials: E
authors.lastname: Donaworth
authors.forename: Brian
authors.initials: B
authors.lastname: Siroky
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications*; D000818:Animals; D017209:Apoptosis; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D051379:Mice; D020127:Recovery of Function; D051437:Renal Insufficiency / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015427:Reperfusion Injury / Q000150:complications*; D013997:Time Factors
chemical_list: D003404:Creatinine; D020784:Matrix Metalloproteinase 8
keywords: Acute kidney injury; chronic kidney injury; matrix metalloproteinase-8; renal failure