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1. |
Research on renal endothelin in proteinuric nephropathies dictates novel strategies to prevent progression |
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Current Opinion in Nephrology and Hypertension,
Volume 10,
Issue 1,
2001,
Page 1-6
Ariela Benigni,
Norberto Perico,
Giuseppe Remuzzi,
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摘要:
Proteinuria is one of the major risk factors for renal disease progression in patients with chronic nephropathies. Studies in disease models have helped to delineate mechanisms leading to renal structural damage as a result of persistent dysfunction of the glomerular barrier to proteins, even when the primary immune or non-immune insult to the kidney has ceased. From these preclinical studies, a role for endothelin in proteinuric chronic renal diseases has been suggested, thus providing the rationale for novel therapeutic approaches with endothelin receptor antagonists to maximize renoprotection so far achieved with blockade of the renin-angiotensin system by angiotensin-converting enzyme inhibition or angiotensin II receptor antagonism. Trials are needed to explore this potential area of clinical interest.
ISSN:1062-4821
出版商:OVID
年代:2001
数据来源: OVID
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2. |
Do matrix metalloproteinases MMP-2 and MMP-9 (gelatinases) play a role in renal development, physiology and glomerular diseases? |
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Current Opinion in Nephrology and Hypertension,
Volume 10,
Issue 1,
2001,
Page 7-12
Brigitte Lelongt,
Bruno Legallicier,
Rémi Piedagnel,
Pierre Ronco,
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摘要:
Metalloproteinases MMP-2 and MMP-9 (also called gelatinases) are involved in cell invasion and in embryonic development and organogenesis. A growing number of reports suggest that MMP-2 and MMP-9 play some role in renal development, renal tubule physiology and glomerular pathophysiology. This editorial will focus on recent controversial data, especially those obtained from studies on MMP-9-deficient mice, which shed new light on the functions of gelatinases in normal and diseased kidneys.
ISSN:1062-4821
出版商:OVID
年代:2001
数据来源: OVID
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3. |
Growing kidneys |
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Current Opinion in Nephrology and Hypertension,
Volume 10,
Issue 1,
2001,
Page 13-17
Marc Hammerman,
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摘要:
The number of kidney transplantations performed per year is restricted by the limited availability of donor organs. One possible solution to this shortage is the use of renal xenografts. However, the transplantation of xenografts is complicated by hyperacute and acute rejection. A second possible solution is to ‘grow a kidney’ from a transplanted renal anlage. It has been postulated that the host immune response might be attenuated after the transplantation of such an anlage (metanephros) instead of a developed kidney. Transplanted metanephroi become chimeric organs in that their blood supply originates, at least partly, from the host. It is possible to transplant a developing metanephros, without the use of immunosuppression, from one rat to another. Transplanted metanephroi grow, differentiate, become vascularized, and function in host rats. ‘Growing kidneys’ via the transplantation of metanephroi may hold promise as a novel therapeutic approach to the treatment of chronic renal failure.
ISSN:1062-4821
出版商:OVID
年代:2001
数据来源: OVID
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4. |
CD2-associated protein and the kidney |
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Current Opinion in Nephrology and Hypertension,
Volume 10,
Issue 1,
2001,
Page 19-22
Andrey Shaw,
Jeffrey Miner,
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摘要:
During the past 3 years there have been significant advances in our understanding of the biology of the glomerular podocyte. In particular, two proteins, CD2-associated protein and nephrin, have been identified as critical podocyte proteins that are both required for normal glomerular filtration. In addition to supporting the idea that the slit diaphragm plays a crucial role in glomerular function, these results suggest novel insights into the pathogenesis of glomerular diseases. The present review addresses these recent advances and discusses the implications of the findings.
ISSN:1062-4821
出版商:OVID
年代:2001
数据来源: OVID
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5. |
Current advances in molecular genetics of autosomal-dominant polycystic kidney disease |
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Current Opinion in Nephrology and Hypertension,
Volume 10,
Issue 1,
2001,
Page 23-31
Guanqing Wu,
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摘要:
Autosomal-dominant polycystic kidney disease results from at least two causal genes,PKD1andPKD2. The identical clinical phenotype in human patients and targetedPkd1andPkd2mutant mouse models provides evidence that both gene products act in the same pathogenic pathway. The discovery of direct PKD1 and PKD2 interactions implies that both gene products, polycystin-1 and polycystin-2, play a functional role in the same molecular complex. The spectrum of germ-line mutations in both genes and the somatic mutations identified from individual PKD1 or PKD2 cysts indicate that loss of function of either PKD1 or PKD2 is the mechanism of cystogenesis in autosomal-dominant polycystic kidney disease. A novel mouse model, Pkd2WS25/−, has proved that loss of heterozygosity is the molecular mechanism of autosomal-dominant polycystic kidney disease. Recently, studies on the expression patterns of PKD1 and PKD2 in humans or mice indicate that polycystin 1 and polycystin 2 seem to have their own respective functional roles, even though most of the functions of these polycystins are parallel during human and mouse development. Pkd2-deficient mice have cardiac septum defects, but Pkd1 knockout mice do not have this phenotype. On the other hand,Pkd2has a very low level of expression in the central nervous system when compared withPkd1. In addition, the level of expression of Pkd1 is increased during mesenchymal condensation, whereas Pkd2 expression is unchanged. Preliminary data have shown that thePKD1/PKD2compound trans-heterozygous has a more severe cystic phenotype in the kidney than that of an age-matched heterozygous type 1 or type 2 of autosomal-dominant polycystic kidney disease alone. This finding suggests that PKD1 may be a modifier of disease severity for PKD2, and vice versa. The characteristics of the contiguous PKD1/TSC2 syndrome phenotypes and the data fromKrdmice imply thatTSC2andPAX2may also serve as potential modifiers for the disease severity of autosomal-dominant polycystic kidney disease.
ISSN:1062-4821
出版商:OVID
年代:2001
数据来源: OVID
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6. |
The roles of cubilin and megalin, two multiligand receptors, in proximal tubule function: possible implication in the progression of renal disease |
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Current Opinion in Nephrology and Hypertension,
Volume 10,
Issue 1,
2001,
Page 33-38
Pierre Verroust,
Renata Kozyraki,
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摘要:
Proteins that have not been retained by the glomerulus are reabsorbed in the proximal tubule by endocytosis, a process that involves binding at the apical pole of the tubule cell, vesicular internalization and subsequent lysosomal degradation. Data presented in this review indicate that the initial recognition step involves two high molecular weight proteins, megalin and cubilin, which have multiligand properties and can therefore account for the wide variety of proteins reabsorbed. Given the potential importance of transepithelial protein traffic in the induction of interstitial fibrosis, the identification of these receptors may have implications in the progression of acute or chronic renal disease and may provide a target for therapeutic intervention.
ISSN:1062-4821
出版商:OVID
年代:2001
数据来源: OVID
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7. |
Sodium reabsorption in aldosterone-sensitive distal nephron: news and contributions from genetically engineered animals |
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Current Opinion in Nephrology and Hypertension,
Volume 10,
Issue 1,
2001,
Page 39-47
François Verrey,
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摘要:
The precise adaptation of renal sodium excretion to systemic needs is to a large extent achieved by the regulation of sodium re-absorption in the aldosterone-sensitive distal nephron. Transcellular sodium re-absorption by the segment-specific cells of the aldosterone-sensitive distal nephron (often called principal cells) is mainly controlled at the level of the expression and activity levels of the epithelial sodium channel, the apical amiloride-sensitive sodium influx pathway. Recent investigations have identified the first early aldosterone-induced proteins that act on epithelial sodium channel function in expression systems. Indirect evidence suggests that one of these aldosterone-induced proteins, the serum- and glucocorticoid-inducible protein kinase SGK1, plays a central integratory role in the control of epithelial sodium channel surface expression and activity, also in the mammalian kidney. Gene-modified animals lacking epithelial sodium channel subunits or expressing mutant subunits have substantiated the central role of the epithelial sodium channel in sodium re-absorption and blood pressure control, as well as for neonatal lung liquid clearance. Mice overexpressing or lacking specific hormones or their receptors have been used to study their role in sodium transport regulation, but the study of mouse physiology appears to lag behind the generation of gene-modified mice. Nonetheless, these new animal models have had a strong impact on research, by stimulating the integration of knowledge and techniques learned from reductionistic molecular approaches into tissue and animal studies, thus breaking down barriers and stimulating collaborations.
ISSN:1062-4821
出版商:OVID
年代:2001
数据来源: OVID
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8. |
Cytokines and hormones with anti-inflammatory effects: new tools for therapeutic intervention |
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Current Opinion in Nephrology and Hypertension,
Volume 10,
Issue 1,
2001,
Page 49-54
Laurent Baud,
Bruno Fouqueray,
Agnès Bellocq,
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摘要:
The inflammation that is involved in the development of glomerulonephritis is tightly regulated by the expression of anti-inflammatory factors. These include circulating hormones, such as glucocorticoids, and mediators that are produced by intrinsic cells and infiltrating leucocytes. The present review focuses on these anti-inflammatory factors, summarizing in particular their activities in existing models of glomerulonephritis. In addition, experimental evidence is presented that anti-inflammatory mediators are able to increase glucocorticoid binding or signalling in target cells. These data help to explain the in-vivo efficacy of anti-inflammatory mediators, and offer a promising new avenue for therapeutic intervention.
ISSN:1062-4821
出版商:OVID
年代:2001
数据来源: OVID
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9. |
Cytokine cross-talk between tubular epithelial cells and interstitial immunocompetent cells |
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Current Opinion in Nephrology and Hypertension,
Volume 10,
Issue 1,
2001,
Page 55-59
Cees van Kooten,
Mohamed Daha,
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摘要:
Immunostaining of renal biopsies of patients with interstitial rejection of allografts or other forms of interstitial inflammation has demonstrated the presence of activated T cells and monocytes/macrophages in the tubulointerstitial area. Cytokines that are produced by infiltrating cells are capable of activating tubular epithelial cells. In turn tubular epithelial cells can produce a wide variety of inflammatory mediators, including chemokines, which further regulate cellular influx. Interfering in this cross-talk between tubular epithelial cells and infiltrating cells might provide new options for therapeutic intervention.
ISSN:1062-4821
出版商:OVID
年代:2001
数据来源: OVID
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10. |
Implications from the Heart Outcomes Prevention Evaluation Study |
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Current Opinion in Nephrology and Hypertension,
Volume 10,
Issue 1,
2001,
Page 61-63
Matthew Weir,
Roland Blantz,
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ISSN:1062-4821
出版商:OVID
年代:2001
数据来源: OVID
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