Protease administration decreases enhanced transforming growth factor-beta 1 content in isolated glomeruli of diabetic rats
| Autor: | Leszek Paczek, Gaciong Z, Bartlomiejczyk I, Sebekova K, Birkenmeier G, Heidland A |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Rutin Body Weight Kidney Glomerulus Organ Size Kidney Function Tests Bromelains Cathepsin B Diabetes Mellitus Experimental Fibronectins Rats Transforming Growth Factor beta1 Drug Combinations Transforming Growth Factor beta Endopeptidases Animals Diabetic Nephropathies Trypsin alpha-Macroglobulins Collagenases Rats Wistar |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0378-6501 |
| Popis: | Overproduction of transforming growth factor (TGF)-beta 1 messenger RNA is of fundamental importance in the pathogenesis of diabetic nephropathy. In vitro studies have recently shown that the serine protease trypsin diminishes the enhanced TGF-beta 1-expression induced by advanced glycation end products. Moreover, proteolytic enzymes may accelerate the removal of TGF-beta 1 from renal tissue via a protease-induced activation of alpha 2-macroglobulin (alpha 2M). This activation results in the binding of numerous cytokines, including TGF-beta 1 and is followed by enhanced plasma clearance of the protease alpha 2M-cytokine complex. In the present study in streptozotocin-diabetic rats we investigated whether the administration of Phlogenzym, a fixed combination of the proteases trypsin and bromelain combined with the antioxidant rutosid, modulates renal hypertrophy and the formation of TGF-beta 1 in isolated glomeruli. Three weeks after induction of diabetes, renal hypertrophy developed with an enhanced kidney/body weight ratio. When compared with normal rats, an elevated content of intraglomerular TGF-beta 1 (44.25 +/- 21.9 vs. 71.1 +/- 23.4 ng/microgram DNA, p0.05) as well as fibronectin (2.62 +/- 0.49 vs. 3.42 +/- 0.62 ng/microgram DNA, p0.05) was observed. In the diabetic rats, treatment with intraperitoneal proteases prevented the rise of intraglomerular TGF-beta 1 content (34.9 +/- 22.2 ng/microgram DNA, p0.01) and attenuated the rise of fibronectin (3.03 +/- 1.12 ng/microgram DNA NS). Furthermore, a decrease in the kidney/body weight ratio (p0.01) was achieved. Protease administration did not affect blood glucose concentration and was without visible adverse effects. |
| Databáze: | OpenAIRE |
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