Molecular mechanisms of renal allograft fibrosis

Waller, J.R.; Nicholson, M. L.

doi:10.1046/j.0007-1323.2001.01867.x

Cited by 55 publications

(46 citation statements)

References 123 publications

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“…However, interstitial fibrosis was found in all the long-term grafts, and so it is uncertain how long the transplants would continue to function. 18 As there was no leakage of fluoresceine into the anterior chamber during angiography, it is probable that the tight junctions have remained intact.…”

Section: Discussionmentioning

confidence: 99%

Prolonged ocular hypotension: would ciliary tissue transplantation help

Watson

Jovanovik-Pandova

2008

Eye

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Aims Ocular hypotony and phthisis bulbi from persistent fistulae, ciliochoridal detachments, or inflammation, that cannot be treated currently. However, complete shutdown of the ciliary epithelium is rare. Secreting, transplanted ciliary tissue could restore the IOP to a level where further visual damage would not occur or even be reversed. Methods Allografts of ciliary epithelium and its substrate were placed on to the surface of the iris of normal albino rabbits. The progress of the transplanted tissue was followed in the untreated animals, those who had been immunosuppressed and those who had been immunosuppresed together with cold whole body perfusion for up to 55 days. Changes were assessed by slit-lamp observation, luconyl blue staining, fluoresceine angiography, and these were compared with the histology and electron microscopic appearances. Results Transplants survived the period of ischaemia in the anterior chamber. They started to be revascularised within 4 days and were completely revascularised in 12 days. Untreated animals showed classical rejection phenomena. However, the ciliary epithelial tissue in those animals who were immunosuppressed and had been subjected to whole body perfusion remained normal and were secreting aqueous, as judged by the histological and electron microscopic appearances. Conclusions Perfused allografts of ciliary tissue will survive in the normal anterior chamber of the immunosuppressed rabbit, and the electron microscopic evidence indicates that the tissue is producing aqueous. If this can be shown to be adequate in the damaged eye, then ciliary transplantation could be a valuable tool in the management of severe intractable hypotony.

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Section: Discussionmentioning

confidence: 99%

Prolonged ocular hypotension: would ciliary tissue transplantation help

Watson

Jovanovik-Pandova

2008

Eye

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“…Tissue repair is initiated by inflammatory and fibrogenetic signaling followed by interstitial mononuclear and macrophage infiltration, and tissue remodeling involves a variable extent of fibroblast proliferation and deposit of extracellular matrix. Ongoing interstitial fibrosis is also known to associate with microvascular injury and loss of interstitial capillaries, followed by tissue hypoxia [139].…”

Section: Co Prevents Fibrosismentioning

confidence: 99%

Protective effect of carbon monoxide in transplantation

Nakao¹

2006

J Cell Mol Med

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During the last decades due to the development of new immunosuppressive agents and improvements in organ preservation methods, surgical techniques, and postoperative care, organ transplantation has become an ultimate therapeutic option for irreversible organ failure. Early graft survival has significantly improved; however, the long-term outcome remains unsatisfactory. Multiple factors, both immunogenic and non-immunogenic etiologies, are involved in the deterioration of the allografts, and the recent use of expanded criteria donors to overcome the organ shortage may also contribute to the graft losses. Carbon monoxide (CO) is commonly viewed as a poison in high concentrations due to its ability to interfere with oxygen delivery. However, CO is endogenously produced in the body as a byproduct of heme degradation by the heme oxygenase (HO) and has recently received notable attention as a gaseous regulatory molecule. In fact, an augmentation of endogenous CO by induction of HO-1 or exogenously added CO is known to have potent cytoprotective effects in various disease models. Several recent reports have demonstrated that CO provides potent cytoprotective effects in the field of organ and cell transplantation. CO is able to prevent ischemia/reperfusion injury, allograft rejection, and xenograft rejection via its anti-inflammatory, anti-apoptotic and anti-proliferation effects, suggesting that CO might be a valuable therapeutic option in the field of transplantation. Based on the recent advancement of our understanding of CO as a new therapeutic molecule, this review attempts to summarize the functional roles as well as biological and molecular mechanisms of CO in transplantation and discusses potential CO application to the clinical transplant setting.

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“…Custom-made multiprobe template sets (BD Biosciences) were chosen to represent renally expressed growth factors, cytokines, chemokines, and matrix modulators that have previously been shown to modulate renal fibrosis (9,30,31). Probe sets used in study B were #62 (vascular endothelial growth factor [VEGF], MCP-1, PDGF-A, TGF-␤ 1 , TGF-␤ 2 , TGF-␤ 3 , TGF-␤R1, TGF-␤R2, bone morphogenic protein 7 , L32, and glyceraldehyde-3-phosphate dehydrogenase [GAPDH]), #84 (matrix metalloprotease-2 [MMP-2], MMP-9, TNF receptor p75 (TNF Rp75), TNF Rp55, macrophage inflammatory protein-2, plasminogen activator inhibitor 1, tissue inhibitor of metalloprotease 1[TIMP1], TIMP2, L32, and GAPDH), and #85 (IL-10, IL-1, IL-12, type 1 collagen, type 2 collagen, TNF-␣, L32, and GAPDH).…”

Section: Multiprobe Rnase Protection Assaymentioning

confidence: 99%

Rapamycin Ameliorates Proteinuria-Associated Tubulointerstitial Inflammation and Fibrosis in Experimental Membranous Nephropathy

Bonegio¹,

Fuhro²,

Wang³

et al. 2005

Journal of the American Society of Nephrology

150

100

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Proteinuria is a risk factor for progression of chronic renal failure. A model of proteinuria-associated tubulointerstitial injury was developed and was used to examine the therapeutic effect of rapamycin. Two studies were performed. In study A, proteinuric rats were given sheep anti-Fx1A to induce experimental membranous nephropathy; control rats received normal sheep serum. Four weeks later, groups were subdivided and underwent laparotomy alone (two kidneys), nephrectomy alone (one kidney), or nephrectomy with polectomy (0.6 kidney). Renal function and morphology were evaluated 4 wk later. Whereas control rats never developed proteinuria, anti-Fx1A induced severe proteinuria. Proteinuria was unaffected by renal mass reduction. Proteinuric rats developed tubulointerstitial disease that was most severe in rats with 0.6 kidneys. Renal function (GFR) was reduced by loss of renal mass and was reduced further in proteinuric rats with 0.6 kidneys. In study B, the effect of rapamycin on the expression of candidate proinflammatory and profibrotic genes and the progression of proteinuria-associated renal disease were examined. All rats received an injection of anti-Fx1A and were nephrectomized and then divided into groups to receive rapamycin or vehicle. Gene expression, renal morphology, and GFR were evaluated after 4, 8, and 12 wk. Rapamycin reduced expression of the proinflammatory and profibrotic genes (monocyte chemotactic protein-1, vascular endothelial growth factor, PDGF, TGF-␤ 1 , and type 1 collagen). Tubulointerstitial inflammation and progression of interstitial fibrosis that were present in vehicle-treated rats were ameliorated by rapamycin. Rapamycin also completely inhibited compensatory renal hypertrophy. In summary, rapamycin ameliorates the tubulointerstitial disease associated with chronic proteinuria and loss of renal mass.

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Molecular mechanisms of renal allograft fibrosis

Cited by 55 publications

References 123 publications

Prolonged ocular hypotension: would ciliary tissue transplantation help

Prolonged ocular hypotension: would ciliary tissue transplantation help

Protective effect of carbon monoxide in transplantation

Rapamycin Ameliorates Proteinuria-Associated Tubulointerstitial Inflammation and Fibrosis in Experimental Membranous Nephropathy

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