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1. |
Applications of cell therapy to whole kidney replacement |
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Current Opinion in Nephrology and Hypertension,
Volume 12,
Issue 1,
2003,
Page 1-3
Marc Hammerman,
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ISSN:1062-4821
出版商:OVID
年代:2003
数据来源: OVID
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2. |
Notch signaling in kidney development |
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Current Opinion in Nephrology and Hypertension,
Volume 12,
Issue 1,
2003,
Page 5-10
Brent McCright,
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摘要:
Purpose of reviewNotch signaling is a highly conserved mechanism used by multicellular animals to specify cell fate decisions during the formation of complex structures such as the kidney. A number of studies have recently identified requirements for Notch signaling during kidney organogenesis and tissue repair. This review will summarize these studies and compare Notch signaling in the mammalian kidney with Notch signaling in other organ systems.Recent findingsA targeted mutation in the mouseNotch2receptor resulted in kidneys that are devoid of glomerular endothelial and mesangial cells. The mutant epithelial cells of the developing glomerulus have reduced amounts of vascular endothelial growth factor expression, which may be responsible for the lack of vascularization observed in these glomeruli.Notch2is expressed in the epithelial cells of the developing glomerulus, and a potential ligand,Jagged1, is expressed in the endothelial cells of the glomerulus. Mice simultaneously heterozygous for mutations in bothNotch2andJagged1phenocopy the kidney defects seen in mice homozygous for theNotch2mutation. These doubly heterozygous mice also display liver and heart developmental abnormalities reminiscent of Alagille's syndrome.SummaryNotch signaling is required for kidney development, and the expression of Notch genes is increased in response to kidney damage. Further studies of Notch signaling will be important in order to understand kidney development and tissue repair.
ISSN:1062-4821
出版商:OVID
年代:2003
数据来源: OVID
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3. |
The signals that drive kidney development: a view from the fly eye |
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Current Opinion in Nephrology and Hypertension,
Volume 12,
Issue 1,
2003,
Page 11-17
Ross Cagan,
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摘要:
Purpose of reviewDevelopment of the mammalian kidney is a complex process involving numerous signals and signaling pathways. Other complex tissues have benefited enormously from studies in lower, simpler organisms. The present review provides an update on what we have learned from the fruitflyDrosophila melanogaster, and argues thatDrosophilais an important but under-utilized organism for study of renal development.Recent findingsThe Malpighian tubules provide renal function to the fly. These require a number of signaling pathways for their development that are also seen in vertebrate kidney development, including the Notch, Ras, and Wnt signaling pathways, as well as nuclear factors such as Krüppel and Cut/Cux-1. Many of these factors are shared between early Malpighian tubule development and ureteric bud formation. The Ret signaling receptor, which is central to mammalian renal development, is poorly understood in flies, although its expression pattern is intriguing. Surprisingly, other signaling factors such as Neph-1, Pax2, and Wilms' tumor suppressor-1 appear to work within later fly retinal development, providing a surprising link between these two disparate tissues.SummaryDrosophilaoffers a powerful palate of tools for dissecting developmental processes. Importantly, these tools can often be examined at the level of single cells, permitting us to address issues of differentiation with high resolution. If we are to take full advantage ofDrosophila, however, then we must target specific issues and gain a better understanding of the details of Malpighian tubule development.
ISSN:1062-4821
出版商:OVID
年代:2003
数据来源: OVID
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4. |
Hoxgenes and kidney patterning |
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Current Opinion in Nephrology and Hypertension,
Volume 12,
Issue 1,
2003,
Page 19-23
Larry Patterson,
S. Potter,
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摘要:
Purpose of reviewHoxgene activity is essential for proper organization or pattern of the vertebrate body plan and is necessary for organogenesis. Sequence conservation within this family of genes is high yet they are involved in very diverse developmental processes. How this family functions in these processes is a challenging question, but is important for the understanding of renal organogenesis. MultipleHoxgenes are expressed in the kidney and mutation in at least one group of paralogous genes results in severe renal defects.Recent findingsRecent studies in mice with targetedHoxgene mutations and in kidney cell lines demonstrate that these genes have evolved to control tissue specific functions through their ability to regulate the expression of renal morphogens. The studies also demonstrate thatHoxgene activity is not only restricted by the domain of expression but also by the specificity of the DNA binding homeodomain. Interestingly, these conserved homeodomains are not wholly interchangeable for normal renal organogenesis while they do appear to be interchangeable for axial skeleton development.SummaryIt is clear thatHoxgenes regulate important interactions between the ureteric bud and metanephric mesenchyme. Nevertheless, much work remains to define the expression patterns of multipleHoxgenes during kidney development, to better determine the functional relationships of the encodedHoxproteins, and to identify additionalHoxdownstream targets.
ISSN:1062-4821
出版商:OVID
年代:2003
数据来源: OVID
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5. |
Tubular epithelial-myofibroblast transdifferentiation mechanisms in proximal tubule cells |
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Current Opinion in Nephrology and Hypertension,
Volume 12,
Issue 1,
2003,
Page 25-29
Hui Lan,
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摘要:
Purpose of reviewEmerging evidence suggests that tubular epithelial-myofibroblast transdifferentiation is an important event in renal tubulointerstitial fibrosis. This review describes the recent findings in the context of the tubular epithelial-myofibroblast transdifferentiation process and discusses the possible mechanisms involved.Recent findingsTubular epithelial-myofibroblast transdifferentiation is a complex process involving disruption of polarized tubular epithelial cell morphology into cells with spindle-shaped mesenchymal morphology, formation of actin stress fibers, loss of cell-cell adhesions through downregulation of E-cadherin, destruction of basement membrane, and increased cell migration and invasion. This phenotypic transition has also been recently reported in human glomerulonephritis with progressive tubulointerstitial fibrosis. Transforming growth factor-β is a key fibrogenic growth factor that regulates tubular epithelial-myofibroblast transdifferentiation, which is counter-regulated by hepatocyte growth factor. In addition, basic fibroblast growth factor, advanced glycation end products, and angiotensin II have also been reported to induce the process. Importantly, the recent discovery of transforming growth factor-β/Smad signaling has allowed the delineation of the intracellular mechanisms of tubular epithelial-myofibroblast transdifferentiation. Indeed, Smad signaling is a key pathway whereby transforming growth factor-β and angiotensin II induce tubular epithelial-myofibroblast transdifferentiationin vitro. This involves the activation of transforming growth factor-β receptor-associated Smad2 and is inhibited by an inhibitory Smad protein, Smad7. Thus, Smad signaling plays a critical role in tubular epithelial-myofibroblast transdifferentiation.SummaryRenal myofibroblasts may be derived from tubular epithelial cells by a process of tubular epithelial-myofibroblast transdifferentiation. Transforming growth factor-β signals through Smads to positively or negatively regulate this process. Blockade of this process by either hepatocyte growth factor or targeting the Smad signaling pathway may provide novel therapeutic strategies to combat renal fibrosis.
ISSN:1062-4821
出版商:OVID
年代:2003
数据来源: OVID
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6. |
Shear-stress-responsive signal transduction mechanisms in renal proximal tubule cells |
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Current Opinion in Nephrology and Hypertension,
Volume 12,
Issue 1,
2003,
Page 31-34
Marie Essig,
Gérard Friedlander,
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摘要:
Purpose of reviewPhenotypic alterations resulting from flow-induced mechanical strains is a growing field of research in many cell types such as vascular endothelial and smooth muscle cells, chondrocytes or osteocytes. Although it has been acknowledged for several decades that tubular flow is a main determinant of tubular behavior in terms of vectorial transport of water and solutes, the effect of flow on other characteristics of proximal tubular cell phenotype was ignored until recently. The purpose of the review is to summarize the various effects of shear-stress, recently demonstrated in renal proximal cells.Recent findingsNew results demonstrate that tubular flow has pleiotropic effects on proximal tubular cells, affecting,in vitroandin vivo, the organization of the cytoskeleton, the synthesis of extracellular matrix proteases and the activity of specific transcription factors.SummaryThese results suggest that flow-induced mechanical strains could be one determinant of tubulointerstitial lesions during the progression of renal diseases.
ISSN:1062-4821
出版商:OVID
年代:2003
数据来源: OVID
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7. |
The parathyroid hormone-related protein system: more data but more unsolved questions |
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Current Opinion in Nephrology and Hypertension,
Volume 12,
Issue 1,
2003,
Page 35-42
Thierry Massfelder,
Jean-Jacques Helwig,
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摘要:
Purpose of reviewThe present review focuses on recent studies that might be considered as the most relevant advances in the parathyroid hormone-related protein field, with special emphasis on proven functions in renovascular and cardiovascular systems, in physiological as well as pathological conditions. Thus, the questions as to whether and how parathyroid hormone-related protein intervenes in vascular development and homeostasis and in vascular diseases such as hypertension, atherosclerosis, restenosis and heart failure have begun to be unraveled.Recent findingsSince its discovery from hypercalcemia-associated tumors in 1987, it has become clear that parathyroid hormone-related protein is a ubiquitously expressed poly-hormone and plays crucial roles in normal life. The early lethality to parathyroid hormone-related protein knockout mice emphasizes the crucial roles of the protein in development but has limited the use of these models. However, data accumulated from transgenic animals overexpressing the protein in particular cells have provided considerable support to its physiological and pathological relevance. The recent demonstration that nascent parathyroid hormone-related protein not only follows the secretory pathways, but also directly translocates to the nucleus, is beginning to uncover new actions for the protein in a number of physiological systems such as bone, mammary gland and vascular smooth muscle, as well as in pathological situations, such as cancer, osteoporosis, sepsis, atherosclerosis and hypertension.SummaryThe development of mice with conditionally deleted parathyroid hormone-related protein or parathyroid hormone-1 receptor alleles will allow the creation of cell- or tissue-specific parathyroid hormone-related protein knockout mice which will greatly facilitate the determination of the biological relevance of this protein in a specific cell or tissue type, particularly in the cardiovascular system.
ISSN:1062-4821
出版商:OVID
年代:2003
数据来源: OVID
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8. |
Vascular endothelial growth factor: a new player in the pathogenesis of renal fibrosis |
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Current Opinion in Nephrology and Hypertension,
Volume 12,
Issue 1,
2003,
Page 43-49
Duk-Hee Kang,
Richard Johnson,
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摘要:
Purpose of reviewThere is new and emerging evidence that renal vascular changes contribute to progressive renal disease and that alteration of vascular endothelial growth factor might play an important role in modulating microvascular loss or macrovascular remodeling in the kidney.Recent findingsMicrovascular endothelial loss both in glomerular and peritubular capillaries of progressive renal disease is directly linked to impaired blood flow, the development of renal ischemia and scarring. Vascular endothelial growth factor is a proliferative survival factor for endothelial cells, which could preserve stressed endothelium or stimulate angiogenesis, stabilize renal function and slow histologic progression as shown in different animal models of progressive renal disease. However, there has been some evidence for the mitogen playing a role in the development and progression of atherosclerosis via a mechanism that amplifies the inflammatory reaction. Whether vascular endothelial growth factor is detrimental in early stages of diabetic nephropathy or other renal conditions is not yet clearly answered.SummaryDespite dramatic progress in current knowledge of vascular biology in progressive renal disease, there are still controversies about the mechanism by which vascular endothelial growth factor works in the kidney in different conditions and at different time points. We suggest it is now time to think of integral effects of this angiogenic factor as a new player in renal fibrosis with its potential therapeutic implication.
ISSN:1062-4821
出版商:OVID
年代:2003
数据来源: OVID
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9. |
The renin receptor: the facts, the promise and the hope |
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Current Opinion in Nephrology and Hypertension,
Volume 12,
Issue 1,
2003,
Page 51-55
Genevieve Nguyen,
Celine Burckle,
Jean-Daniel Sraer,
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摘要:
Purpose of reviewThe renin-angiotensin system plays a major role in the control of blood pressure and of salt balance, but it is also involved in physiological and pathological processes, development, inflammation and cardiac hypertrophy. A concept has emerged suggesting that these effects are due to a local activation of the renin-angiotensin system. The search for a receptor of renin was based on the idea that tissue (pro)renin is taken up from the circulation and on data suggesting that reninper sehas cellular effects independent of angiotensin II.Recent findingsEndothelial cells and cardiac myocytes bind (pro)renin via the mannose-6-phosphate receptor, mainly a clearance receptor as no cellular effect has been specifically attributed to prorenin binding. A functional receptor was cloned recently. It mediates intracellular signalling by activating the mitogen activated protein kinases, extracellular signal regulated kinases 1 and 2, and acts as a co-factor by increasing the efficiency of angiotensinogen cleavage by receptor-bound (pro)renin. The receptor is abundantly expressed in heart, brain, placenta and eye, compared with a lower expression in liver and kidney. In normal human kidney and heart, it is localized in the mesangium and in the coronary and kidney artery, associated with smooth-muscle cells and co-localized with renin.SummaryThis receptor provides a functional role for prorenin and may help to understand the physiological and pathological role of elevated levels of prorenin and of local activation of the renin-angiotensin system. From a practical point of view, it questions the need for a pharmacological compound blocking (pro)renin binding and activity as an alternative to the classical inhibitors of the renin-angiotensin system.
ISSN:1062-4821
出版商:OVID
年代:2003
数据来源: OVID
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10. |
Blood pressure and cardiovascular risks: implications of the presence or absence of a nocturnal dip in blood pressure |
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Current Opinion in Nephrology and Hypertension,
Volume 12,
Issue 1,
2003,
Page 57-60
Matthew Weir,
Roland Blantz,
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ISSN:1062-4821
出版商:OVID
年代:2003
数据来源: OVID
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