ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Erythropoietin has been demonstrated to improve the quality of life in patients with chronic renal failure, and growth hormone has been approved for use in children with chronic renal failure and short stature as a growth promoting agent. Growth factors also have great therapeutic potential to improve glomerular function in the setting of chronic renal failure. Further studies are required to delineate the role of insulin-like growth factor I in the setting of end-stage chronic renal failure.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Calcification is a component of vascular disease that usually occurs in concert with atheroma formation but through distinct pathophysiological processes. Vessel wall osteoprogenitor cells known as calcifying vascular cells can form bone matrix proteins and calcified nodules, analogous to osteoblastic differentiation in bone. These cells have been isolated from the tunica media of bovine and human arteries, and both in-vitro tissue culture models and mouse models of vascular calcification have been established. Studies of the effects of diabetes mellitus, hyperlipidemia, estrogens and glucocorticoids on calcifying vascular cell function provide insight into the relationship between common human disease states and vascular calcification.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Renal synthesis of the active form of vitamin D, 1,25-dihydroxyvitamin D3[1,25(OH)2D3], is a pivotal step in calcium and phosphate homeostasis. Production of 1,25(OH)2D3is catalyzed by the mitchondrial cytochrome P450, 25-hydroxyvitamin D3-1α-hydroxylase (1α-HYD). As a consequence of the tight regulation of vitamin D metabolism during normal physiology, studies of the expression and regulation of 1α-HYD have proved remarkably difficult. However, the recent cloning of the gene for 1α-HYD has enabled a more comprehensive analysis of the tissue distribution of 1α-HYD, as well as the mechanisms involved in controlling 1,25(OH)2D3production. In particular, an understanding of site-specific expression and regulation of 1α-HYD along the nephron might help to elucidate a more versatile role for 1,25(OH)2D3in renal physiology.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Renal cyclooxygenase-1 and cyclooxygenase-2 actively metabolize arachidonate to metabolism five primary prostanoids: prostaglandin E2, prostaglandin F2a, prostaglandin I2, thromboxane A2, and prostaglandin D2. These lipid mediators interact with a family of distinct G-protein-coupled prostanoid receptors designated EP, FP, IP, TP, and DP, respectively, which exert important regulatory effects on renal function. The intrarenal distribution of these prostanoid receptors has been mapped and the consequences their activation are being characterized. The FP, TP, and EP1receptors preferentially couple to increased cell Ca2+. EP2, EP4, DP, and IP receptors stimulate cyclic adenosine monophosphate, whereas the EP3receptor preferentially couples to Gi, inhibiting cyclic adenosine monophosphate generation. EP1and EP3messenger RNA expression predominate in the collecting duct and thick limb, respectively, where their stimulation reduces sodium chloride and water absorption, promoting natriuresis and diuresis. Interestingly, only a mild change in renal water handling is seen in the EP3receptor knockout mouse. Although only low levels EP2receptor messenger RNA are detected in kidney and its precise intrarenal localization is uncertain, mice with targeted disruption of the EP2receptor display salt-sensitive hypertension, suggesting it also plays an important role in salt excretion. In contrast, EP4messenger RNA is readily detected in the glomerulus where it may contribute to the regulation of renin release and decrease glomerular resistance. TP receptors are also highly expressed in the glomerulus, where they may increase glomerular vascular resistance. The IP receptor messenger RNA is most highly expressed in the afferent arteriole and it may also modulate renal arterial resistance and renin release. At present there is little evidence for DP receptor expression in the kidney. Together these receptors act as physiologic buffers that protect the kidney from excessive functional changes during periods of physiologic stress. Loss of the combined effects of these receptors contributes to the side effects seen in the setting of nonsteroidal anti-inflammatory drug administration, whereas selective antagonists for these receptors may provide new therapeutic approaches in disease.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The present review focuses on recent data regarding the role of endothelin as a mediator of renal vascular fibrosis. Following a brief description of the endothelin system, the question of whether endothelin is involved in hypertensive mechanisms is examined in experimental, genetic and transgenic animal models. Evidence is provided that implicates endothelin as an important factor of the development of tissue fibrosis and end-organ damage associated with hypertension, with particular emphasis on renal vascular fibrosis. Data indicating that endothelin interacts with other vasoconstrictor systems, such as angiotensin II, are also considered. Finally, results from preliminary clinical studies using endothelin receptor antagonists to treat cardiac and renal pathologies are briefly discussed.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Homeodomain-containing transcription factors are essential for a variety of processes in vertebrate development, including organogenesis. They have been shown to regulate cell proliferation, pattern segmental identity and determine cell fate decisions during embryogenesis. During nephrogenesis, homeobox genes play an important role at multiple developmental stages, from the early events in intermediate mesoderm to terminal differentiation of glomerular and tubular epithelia. Increasingly sophisticated genetic approaches will probably reveal additional functions for this class of transcription factors in the developing kidney and lead to the identification of critical downstream target genes.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

It has recently been shown that mesangial cells are subjected to multiple forms of mechanical strain (fluid shear, hydrostatic pressure, and triaxial stretch) as a result of forces exerted by the vasculature. Nevertheless, the exact nature and the relative response to these stimuli have not been clarified. Although it is now well established that cyclic stretching of mesangial cells in culture results in the overproduction of extracellular matrix, indicating how intraglomerular hypertension may lead to glomerular scar formation, the contribution of different intracellular signalling mechanisms and extracellular mediators of the response are only now being identified. Recent studies point to a role for high glucose concentrations, transforming growth factor beta and its receptors, vascular endothelial growth factor, and connective tissue growth factor as important mediators, or modifiers of the response to mechanical strain. Although evidence exists for a role for protein kinase C, recent studies also implicate the mitogen-activated protein kinases along with enhanced DNA-binding activity of AP-1 as part of the signalling cascade altering matrix synthesis and cell proliferation in response to stretch. Finally, recent studies examining the effects of oscillating hyperbaric pressure demonstrate similarities, as well as differences, in comparison to those of cyclic stretch.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Mechanical stresses appear to play a key role in the progression of glomerular diseases that are characterized by increased transcapillary hydraulic pressure. Glomerular mesangial cells proliferate and produce extracellular matrix proteinsin vivoin such diseases. Mesangial cell responses to pulsatile mechanical stimuli have been studied extensivelyin vitroduring the past few years. Mechanical signals are sensed at the cell membrane and propagated through the cytoplasm, and result in the activation of transcription factors that elicit production of prosclerotic cytokines and matrix proteins, and cell proliferation. Endothelial cells are exposed to shear and pulsatile stress and show some similar responses in other vascular beds.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID