Possible role of Ets-1 and MMP-1 in matrix remodeling in experimental cisplatin nephropathy

Nazneen, Arifa; Liu, Diange; Taguchi, Takashi

doi:10.1007/s007950200028

Cited by 15 publications

(10 citation statements)

References 32 publications

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“…In the kidneys of cisplatin-treated rats, the expression of MMP-1 has shown to increase in early stages (on day 3) of cisplatin nephropathy, while the expression decreased in later stages (on day 14). Decreased renal expression of MMP-1 has been shown to be associated with increased interstitial accumulation of type III collagen in kidneys of cisplatin-treated rats [67], suggesting a pathological role of MMPs in cisplatin-nephropathy.…”

Section: Fibroproliferative Eventsmentioning

confidence: 99%

Cisplatin-Associated Nephrotoxicity and Pathological Events

Taguchi

Nazneen

Abid

et al. 2005

Contributions to Nephrology

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236

141

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Cisplatin (cis-diamminedichloroplatinum(II)) is an effective chemotherapeutic agent, and is successfully used in the treatment of a wide range of tumors. Despite its effectiveness as an anti-tumor drug, nephrotoxic side effects have significantly restricted its clinical use. Tubular epithelial cell deletion following cisplatin treatment is a major cause of renal injury. Oxidative stress significantly contributes to cisplatin-associated cytotoxicity, and use of antioxidants could counteract such cytotoxic effects of cisplatin. The renal microenvironmental changes following cisplatin treatment is a complex process and could be broadly categorized into three main pathological events, which at times might overlap: initial cytotoxic events, inflammatory events and fibroproliferative events. Stress responses and heat shock proteins generated following cisplatin treatment are actively involved in the initiation and progression of these events. In this article, we will briefly summarize factors involved in various phases of cisplatin-induced renal injuries.

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Section: Fibroproliferative Eventsmentioning

confidence: 99%

Cisplatin-Associated Nephrotoxicity and Pathological Events

Taguchi

Nazneen

Abid

et al. 2005

Contributions to Nephrology

Self Cite

236

141

View full text Add to dashboard Cite

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“…32 Throughout the literature, attempts to visulalise MMPs and TIMP by immunohistochemistry both in the kidney and in other tissues, as well as our own attempts, including in situ MMP activity assays, have consistently demonstrated the vast bulk of MMPs and TIMPs in an intracellular cytoplasmic location. 22,[33][34][35][36][37] This conflicts with the perceived primary location ascribed to MMPs and TIMPs, which is based predominantly on in vitro cell culture studies that have positioned the MMP/TIMP system as extracellular owing to its function in ECM degradation and matrix remodeling as well as adhesion. 38,39 Therefore, we would have expected to find both MMPs and TIMPs mainly in the interstitium.…”

Section: Discussionmentioning

confidence: 99%

Changes in Matrix Metalloproteinases and Their Inhibitors in Kidney Transplant Recipients

Ak¹,

Nahas²,

Ts³

2012

Exp Clin Transplant

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Objectives: Chronic allograft nephropathy remains one of the main causes of late graft loss after kidney transplant owing to multifactorial development of kidney scarring. Chronic allograft nephropathy is characterised by an excess accumulation of extracellular matrix. A key system regulating extracellular matrix homeostasis are matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases. This study sought to determine if a change in the matrix metalloproteinases/tissue inhibitors of matrix metalloproteinases system contributes to chronic allograft nephropathy-associated progressive kidney scarring. Materials and Methods: Examination of sequential renal biopsies was done at implantation, acute rejection, and subsequent chronic allograft nephropathy. In situ localisation of matrix metalloproteinase activity was assessed with a high-resolution in situ zymography technique using gelatin and collagen 1 substrates. Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases were localised using immunohistochemistry. Results: In situ zymography showed over a 50% reduction in matrix metalloproteinase activity against both collagen 1 and gelatin substrates in chronic allograft nephropathy biopsies. A similar loss of matrix metalloproteinase activity was seen in the glomerular and tubulointerstitial compartments.Immunoreactive matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases were observed intracellularly in mesangial and tubular epithelial cells. Matrix metalloproteinases-1, -2, -3, and -9 were significantly reduced in acute rejection and later in chronic allograft nephropathy. However, glomerular matrix metalloproteinases 1 and 9 and tubulointerstitial matrix metalloproteinase-2 were reduced at implantation. Tissue inhibitors of matrix metalloproteinase-2 and -3 were elevated from implantation onwards. We were unable to stain reproducibly for tissue inhibitors of matrix metalloproteinase-1. Conclusions: Kidney scarring underlying chronic allograft nephropathy is associated with a reduction in matrix metalloproteinases activity that may be due to reduced expression of matrix metalloproteinases -1, -2, -3, and -9, and upregulation of tissue inhibitors of matrix metalloproteinases -2 and -3. Some of these changes originate from implantation.

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“…Bu çalışmada azalmış Ets-1 ve MMP-1 düzeyleri ile artmış interstisiyel birikim arasında ilişkili saptanmıştır. Bu sonuç, Ets-1, MMP-1 ve tip 4 kollajenin moleküler etkileşmesinin sisplatin nefropatisindeki matriks yeniden yapılanmasında rol oynayabileceğini desteklemektedir (14).…”

Section: Türk Nefroloji Diyaliz Ve Transplantasyon Dergisi Turkish Neunclassified

The Role of Matrix Metalloproteinases in Renal Diseases

Sağlam¹

2010

Turk Neph Dial Transpl

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özMatriks 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.anaHTaR SözCÜKlER: Böbrek hastalıkları, Hücre dışı matriks aBSTRaCT 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 whi...

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Possible role of Ets-1 and MMP-1 in matrix remodeling in experimental cisplatin nephropathy

Cited by 15 publications

References 32 publications

Cisplatin-Associated Nephrotoxicity and Pathological Events

Cisplatin-Associated Nephrotoxicity and Pathological Events

Changes in Matrix Metalloproteinases and Their Inhibitors in Kidney Transplant Recipients

The Role of Matrix Metalloproteinases in Renal Diseases

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