Kidney and Blood Pressure Research

Original Paper

Suppressed Activities of Cathepsins and Metalloproteinases in the Chronic Model of Puromycin Aminonucleoside Nephrosis

Huang S.a · Schaefer R.M.b · Reisch S.a · Paczek L.c · Schaefer L.b · Teschner M.a · Sebekova K.d · Heidland A.a

Author affiliations

aFaculty of Medicine, University of Würzburg, and bDepartment of Internal Medicine, University of Münster, Germany; cTransplantation Institute, University of Warsaw, Poland; dInstitute of Preventive and Clinical Medicine, Bratislava, Slovakia

Keywords: GlomerulosclerosisTubulointerstitial fibrosisCathepsinsCollagenaseGelatinase

Related Articles for ""
Kidney Blood Press Res 1999;22:121–127
https://doi.org/10.1159/000025917

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: June 25, 1999
Issue release date: 1999

Number of Print Pages: 7
Number of Figures: 3
Number of Tables: 3

ISSN: 1420-4096 (Print)
eISSN: 1423-0143 (Online)

For additional information: https://www.karger.com/KBR

Abstract

Glomerulosclerosis and tubulointerstitial fibrosis are the hallmarks of chronic renal diseases. In the present study, we have investigated the potential involvement of various proteinases in these alterations in the model of puromycin aminonucleoside (PAN) nephrosis. Two groups of male Wistar rats were given either three or seven injections of PAN (2.0 mg/100 g body weight) over a 4– and 12–week period, respectively. The two control groups received saline injections. Activities of cathepsins (B, H and L) were determined in isolated glomeruli and proximal tubules. Moreover, collagenaselike and gelatinaselike activities were analyzed in isolated glomeruli. Three weeks after weekly PAN injection, the rats developed heavy proteinuria (140.8±22.0 vs. 13.5±3.29 mg/day; p<0.001), and at week 11 protein excretion reached 606.6±23.00 vs. 22.8±1.5 mg/day. Renal morphology revealed minimal glomerular mesangial changes at the 4th week after PAN administration. At the 12th week a marked mesangial matrix accumulation as well as severe tubulointerstitial infiltration and fibrosis associated with tubular dilation and atrophy were observed. Glomerular cathepsins B, H, and L and gelatinaselike activities decreased at the 4th week after the first PAN injection and remained at this low level throughout the entire study period. Glomerular collagenaselike activity decreased at the 4th week (p<0.05) and was still mildly lower than that of the control group at the 12th week, but without significance. In the isolated proximal tubules, the activities of cathepsins B, H, and L showed the same pattern of decreases as those found in the glomeruli over the whole experimental period. Taken together, our data in the model of chronic PAN nephrosis suggest that the suppressed activities of cathepsins as well as the decreased gelatinase– and collagenaselike activities participate in the accumulation of extracellular matrix and thereby may contribute to the development of glomerulosclerosis and tubulointerstitial fibrosis.



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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: June 25, 1999
Issue release date: 1999

Number of Print Pages: 7
Number of Figures: 3
Number of Tables: 3

ISSN: 1420-4096 (Print)
eISSN: 1423-0143 (Online)

For additional information: https://www.karger.com/KBR

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1999, Vol.22, No. 3

1999

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