Fibrosis-associated gene expression in renal transplant glomeruli after acute renal allograft rejection

Brook, Nicholas R.; White, Steve; Waller, J.R.; Bicknell, G R; Nicholson, Michael L.

doi:10.1002/bjs.4133

Cited by 4 publications

(2 citation statements)

References 24 publications

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“…For instance, in 3D cultures of fibroblasts in stressed collagen gels, tenascin‐C is increased in comparison with unrestrained, floating gels (Chiquet‐Ehrismann et al, 1994). Furthermore, the presence of fibrotic foci within breast primary tumors may be associated in many cases with their ability to form metastases (Colpaert et al, 2001; Akiri et al, 2003) and tenascin‐C expression can be correlated with fibrosis in many organs (Kaarteenaho‐Wiik et al, 2000; Brook et al, 2003; El‐Karef et al, 2007). Although direct proof for this is missing, these independent studies lead us to the proposal that tumor stiffness, tumor invasion and tenascin‐C expression are tightly linked parameters.…”

Section: Perspectivesmentioning

confidence: 99%

Tenascins and their implications in diseases and tissue mechanics

Brellier

Tucker

Chiquet‐Ehrismann

2009

Scandinavian Med Sci Sports

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Tenascins are glycoproteins found in the extracellular matrix (ECM) of many tissues. Their role is not only to support the tissue structurally but also to regulate the fate of the different cell types populating the ECM. For instance, tenascins are required when active tissue modeling during embryogenesis or re-modeling after injury occurs. Interestingly, the four members of the tenascin family, tenascin-C, -X, -R and -W, show different and often mutually exclusive expression patterns. As a consequence, these structurally related proteins display distinct functions and are associated with distinct pathologies. The present review aims at presenting the four members of the tenascin family with respect to their structure, expression patterns and implications in diseases and tissue mechanics.

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Section: Perspectivesmentioning

confidence: 99%

Tenascins and their implications in diseases and tissue mechanics

Brellier

Tucker

Chiquet‐Ehrismann

2009

Scandinavian Med Sci Sports

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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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Oxidative stress and glutathione in TGF-β-mediated fibrogenesis

Liu

Pravia

2010

Free Radical Biology and Medicine

407

338

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Transforming growth factor beta (TGF-β) is the most potent and ubiquitous profibrogenic cytokine and its expression is increased in almost all the fibrotic diseases and in experimental fibrosis models. TGF-β increases ROS production and decreases the concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, in various types of cells, which mediates many of TGF-β’s fibrogenic effects. A decreased GSH concentration is also observed in human fibrotic diseases and in experimental fibrosis models. Although the biological significance of GSH depletion in the development of fibrosis remains obscure, GSH and N-acetylcysteine (NAC), a precursor of GSH, have been used in clinics for the treatment of fibrotic diseases. This review summarizes recent findings in the field to address the potential mechanism whereby oxidative stress mediates TGF-β’s fibrogenesis and the potential therapeutic values of antioxidant treatment in fibrotic diseases.

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Fibrosis-associated gene expression in renal transplant glomeruli after acute renal allograft rejection

Abstract: These results suggest that acute rejection episodes do not increase the expression of fibrosis-associated genes in glomeruli from renal transplant biopsies.

Cited by 4 publications

References 24 publications

Tenascins and their implications in diseases and tissue mechanics

Tenascins and their implications in diseases and tissue mechanics

Changes in Matrix Metalloproteinases and Their Inhibitors in Kidney Transplant Recipients

Oxidative stress and glutathione in TGF-β-mediated fibrogenesis

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