Plasmin is not protective in experimental renal interstitial fibrosis1

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Plasmin is not protective in experimental renal interstitial fibrosis1 Kristy L. Edgtton, Renae M. Gow, Darren J. Kelly, Peter Carmeliet, A. Richard Kitching Kidney International Volume 66, Issue 1, Pages 68-76 (July 2004) DOI: 10.1111/j.1523-1755.2004.00707.x Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 1 Renal histopathology in plg+/+ and plg-/- mice. Interstitial renal fibrosis developed in both plasminogen-intact and plasminogen-deficient mice. Disease was moderate at day 7 in both plg+/+ mice (A) and plg-/- mice (B), and severe at day 21, again in both plg+/+ mice (C) and plg-/- mice (D) (high power, ×400, Sirius red stain, collagen appearing red). Kidney International 2004 66, 68-76DOI: (10.1111/j.1523-1755.2004.00707.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 2 Accumulation of collagen in normal contralateral and obstructed kidneys from plg+/+ and plg-/- mice. Hydroxyproline assay demonstrates no difference at 7 days (A) and a small but significant reduction in collagen accumulation at day 21 (B) *P = 0.04. The dotted lines represent values for unobstructed normal mice on which operations have had not been performed. Kidney International 2004 66, 68-76DOI: (10.1111/j.1523-1755.2004.00707.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 3 Macrophage infiltrate in obstructed kidneys from plg+/+ and plg-/- mice. Photomicrographs of interstitial macrophages. At 7 days there was a moderately dense macrophage infiltrate in both plg+/+ (A) and plg-/- (B). At 21 days, the infiltrate in plg+/+ mice (C) was more dense than in plg-/- mice (D) (medium power, ×200, F4/80+ cells, black reaction product, nuclear fast red counterstain). (E) Semiquantitative analysis of macrophage infiltration, showing reduced infiltration at 21 days in mice deficient in plasminogen. Kidney International 2004 66, 68-76DOI: (10.1111/j.1523-1755.2004.00707.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 4 Analysis of transforming growth factor-β1 (TGF-β1) and βig-h3 mRNA in obstructed kidneys from plg+/+ and plg-/- mice at 7 and 21 days. TGF-β1 and βig-h3 mRNA are compared with the housekeeping gene 18S, with the βig-h3:TGF-β1 mRNA ratio providing an index of active to total TGF-β. Results are expressed in arbitrary units (AU) relative to plg+/+ mice at day 7. (A) There was a trend, but no significant difference (P = 0.114) to increased TGF-β1 mRNA at day 7, that was not continued at day 21. (B) There was no significant reduction in βig-h3 mRNA (P = 0.11 at 21 days). (C) There was a strong trend (P = 0.057 at either time point) to reduced βig-h3:TGF-β1 mRNA ratios in plg-/- mice. Kidney International 2004 66, 68-76DOI: (10.1111/j.1523-1755.2004.00707.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 5 Gelatin zymography showing pro-matrix metalloproteinase (MMP)-9 and active MMP-9, and pro-MMP-2 and active MMP-2 activity in kidneys from plg+/+ and plg-/- mice. Pro-MMP-2 but not active MMP-2 activity is measurable in contralateral kidneys and active MMP-2 is increased in obstructed kidneys from plg+/+ mice, but to a lesser degree in plg-/- mice. Plasmin is not required for MMP-9 activation. Representative samples from each group of mice were chosen. Kidney International 2004 66, 68-76DOI: (10.1111/j.1523-1755.2004.00707.x) Copyright © 2004 International Society of Nephrology Terms and Conditions