TITLE

Plasmin is not protective in experimental renal interstitial fibrosis

AUTHOR(S)
Edgtton, Kristy L.; Gow, Renae M.; Kelly, Darren J.; Carmeliet, Peter; Kitching, A. Richard
PUB. DATE
July 2004
SOURCE
Kidney International;Jul2004, Vol. 66 Issue 1, p68
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Plasmin is not protective in experimental renal interstitial fibrosis. Background. The plasminogen-plasmin system has potential beneficial or deleterious effects in the context of renal fibrosis. Recent studies have implicated plasminogen activators or their inhibitors in this process. Methods. The development of renal interstitial fibrosis was studied in mice genetically deficient in plasminogen ( plg−/− mice) and littermate controls ( plg+/+ mice) by inducing unilateral ureteric obstruction (UUO) by ligating the left ureter. Results. Collagen accumulation in the kidney was decreased in plg−/− mice at 21 days compared with plg+/+ mice by hydroxyproline assay ( plg+/+ 19.0 ± 1.2 μg collagen/mg tissue, plg−/− 15.6 ± 0.5 μg collagen/mg tissue, P= 0.04). Macrophage accumulation in plg−/− mice was reduced at 21 days, consistent with a role for plasmin in macrophage recruitment in this model. Myofibroblast accumulation, assessed by the expression of α-smooth muscle actin (α-SMA), was similar in both groups at both time points. Endogenous plasmin played a role in the activation of transforming growth factor-β (TGF-β), as plg−/− mice had lower ratios of βig-h3:TGF-β1 mRNA than plg+/+ mice. Matrix metalloproteinase (MMP)-9 activity was unchanged in the absence of plasmin, but MMP-2 activity was decreased. Conclusion. Plasminogen, the key proenzyme in the plasminogen-plasmin system, does not protect mice from experimental interstitial fibrosis and may have significant pathogenetic effects. These findings, together with other recently published studies in the biology of renal fibrosis, imply that effects of proteins such as plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator receptor (uPAR) on renal fibrosis occur independently from the generation of plasmin.
ACCESSION #
13347252

 

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