A possible role for metalloproteinases in renal cyst development

• Verfasst von: Obermüller, Nicholas [VerfasserIn]
• Verfasst von: Morente Medina, Natividad [VerfasserIn]
• Verfasst von: Kränzlin, Bettina [VerfasserIn]
• Verfasst von: Gretz, Norbert [VerfasserIn]
• Verfasst von: Witzgall, Ralph [VerfasserIn]
• Titel: A possible role for metalloproteinases in renal cyst development
• Verf.angabe: Nicholas Obermüller, Natividad Morente, Bettina Kränzlin, Norbert Gretz, and Ralph Witzgall
• E-Jahr: 2001
• Jahr: [1 Mar 2001]
• Umfang: 11 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 28.06.2022
• Titel Quelle: Enthalten in: American journal of physiology. Renal physiology
• Ort Quelle: Bethesda, Md. : Soc., 1977
• Jahr Quelle: 2001
• Band/Heft Quelle: 280(2001), 3 vom: März, Seite F540-F550
• ISSN Quelle: 1522-1466
• DOI: doi:10.1152/ajprenal.2001.280.3.F540
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: autosomal-dominant polycystic kidney disease
• Sach-SW: extracellular matrix
• Sach-SW: matrix metalloproteinase-14
• Sach-SW: therapy
• Sach-SW: tissue inhibitor of metalloproteinases-2
• Sach-SW: transforming growth factor-β2
• K10plus-PPN: 1808025792

Abstract

The expansion of cysts in polycystic kidneys bears several similarities to the invasion of the extracellular matrix by benign tumors. We therefore hypothesized that cyst-lining epithelial cells produce extracellular matrix-degrading metalloproteinases and that the inhibition of these enzymes may represent a potential target for therapeutic intervention. Using in situ hybridization, we first analyzed the expression of membrane-type metalloproteinase 1 (MMP-14), an essential matrix metalloproteinase, of its inhibitor TIMP-2, and of the cytokine transforming growth factor (TGF)-β2 in the (cy/+) rat model of autosomal-dominant polycystic kidney disease. Upregulated MMP-14 mRNA was predominantly located in cyst-lining epithelia and distal tubules, whereas TIMP-2 mRNA was confined almost exclusively to fibroblasts. TGF-β2, a cytokine known to regulate the expression of matrix metalloproteinases and their inhibitors, was also expressed by cyst wall epithelia. We then treated (cy/+) rats with the metalloproteinase inhibitor batimastat for a period of 8 wk. The treatment with the metalloproteinase inhibitor batimastat resulted in a significant reduction of cyst number and kidney weight. Our study suggests that metalloproteinase inhibitors represent a new therapeutic tool against polycystic kidney disease, which should be applicable independently of the background of the disease.