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Matriks Metaloproteinazların Böbrek Hastalıklarındaki Rolü

The Role of Matrix Metalloproteinases in Renal Diseases

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DOI: 
10.5262/tndt.2011.1002.01

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Abstract (2. Language): 
Matrix metalloproteinases (MMPs) are a family of zinc dependent proteinases and the main promoters of extracellular matrix degradation. Their role in renal diseases is now being understood better. Several progressive renal diseases are characterized with persistent cell proliferation and abnormal production of extracellular matrix by mesengial cells. Understanding mesengial cell proliferation and the factors regulating extracellular matrix metabolism is therefore becoming more important. MMPs have been shown to be produced and excreted from renal glomerular cells and interstitital fibroblast and tubuloepithelial cells have also been shown to excrete MMPs. MMPs function in expansive cell behaviour, embryonic evolution and tissue fibrosis. Production of MMPs are known to increase in inflammation and restructure processes. Data obtained from both experimental and clinical studies has shown the role of MMPs in proliferative glomerulonephritis, hypertensive nephropathy, diabetic nephropathy, HIV nephropathy, toxic nephropathy, obstructive nephropathy, renal cell carcinoma, chronic allograft nephropathy-related fibrosis and in many other renal diseases. In light of these data, therapy options targeting MMPs have become a current issue. Limited data obtained from recent studies are promising about the clinical use of therapies repressing MMPs in future. The roles of MMPs which increase in inflammation and restructure processes in renal diseases and future therapy options are discussed in this review.
Abstract (Original Language): 
Matriks metaloproteinazlar (MMP) çinko bağımlı, geniş bir aileye mensup enzimler olup, hücre dışı matriks yıkımının ana düzenleyicileridirler ve böbrek hastalıklarındaki rolleri giderek daha iyi anlaşılmaktadır. Birçok ilerleyici böbrek hastalığı, süregen hücre çoğalması ve mezengiyal hücreler tarafından hücre dışı matriksin anormal yapımı ile karakterizedir. Bu nedenle mezengiyal hücre çoğalması ve hücre dışı matriks metabolizmasını düzenleyen faktörlerin bilinmesi önem kazanmaktadır. Böbrek glomerüler hücrelerinde MMP’lerin üretilip salındığı, interstisiyel fibroblast ve tubüloepitelyal hücrelerin de MMP salgıladığı gösterilmiştir. MMP’ler böbrekteki yayılımcı hücre davranışı, embriyonik gelişim ve doku fibrozisi olaylarında görev alırlar. Yangı ve yeniden yapılanma işlemlerinde de MMP’lerin yapımlarının arttığı bilinmektedir. Gerek deneysel, gerekse klinik çalışmalardan elde edilen veriler sonucunda; proliferatif glomerülonefritler, hipertansif nefropati, diyabetik nefropati, HİV nefropatisi, toksik nefropati, obstrüktif nefropati, renal hücreli karsinom, kronik allograft nefropati ilişkili fibrozis ve daha birçok böbrek hastalığında MMP’lerin rolleri gösterilmiştir. Bu veriler eşliğinde, MMP’leri hedef alan tedavi seçenekleri gündeme gelmiştir. Yakın zamanlı çalışmalarda elde edilen sınırlı sayıdaki bulgular; MMP baskılayıcı tedavilerin gelecekte klinik uygulamalarda yer almaları konusunda umut verici görünmektedir. Bu derlemede yangı ve yeniden yapılanma işlemlerinde yapımları artan MMP’lerin, böbrek hastalıklarındaki rolleri ve gelecekteki tedavi seçenekleri tartışılacaktır.
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