摘要:

Injury mechanisms activated by the hemodynamic adaptations to nephron loss are considered to represent a final common pathway that underlies the progressive nature of chronic renal disease. In this article, we review experimental evidence that the induction of cell adhesion molecule, cytokine and profibrotic growth factor gene expression and the resultant renal infiltration by inflammatory cells, especially macrophages, are important components of these common pathway mechanisms. Interventions aimed at inhibiting these mechanisms may offer new treatments for slowing or arresting the progression of chronic renal disease.

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

摘要:

The epithelial calcium channel present in the apical membrane of 1,25-dihydroxyvitamin D3-responsive nephron segments represents the first member of a new family of calcium channels. This review covers the distinctive properties of this highly calcium-selective channel and highlights the implications for our understanding of the process of calcium reabsorption.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The identification of a putative apical Ca++channel in 1,25dihydroxyvitamin D3responsive epithelia (proximal intestine and the distal nephron) as well as recent studies using calbindin-D28kknock-out mice indicating the first direct in-vivo evidence for a role for this calcium-binding protein in renal calcium absorption suggest mechanisms, which had remained incomplete, related to the control of renal calcium absorption.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Crystals of calcium oxalate and calcium phosphate bind to anionic molecules on the apical surface of renal collecting duct cells. Atomic arrays on crystal faces interact stereospecifically with cell-surface anions to bind crystals that nucleate in tubular fluid, or those that nucleate directly on the plasma membrane. The internalization of adherent crystals, changes in gene expression, and secretion of specific proteins ensue, and appear to be important processes in crystal retention and kidney stone pathogenesis.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Normal endochondral bone development requires temporal and spatial coordination of various cell types. Parathyroid hormone-related peptide and Indian hedgehog interact with each other and form a feedback loop that plays a major role in this coordination. Defects in the signalling of either of the two molecules cause severe bone malformations.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Adynamic bone disease is emerging as a major type of renal osteodystrophy in chronic dialysis patients. Relative hypoparathyroidism is one of the important abnormalities underlying this disease. Recently, several reports have suggested that hypoparathyroidism reflects, at least in part, a state of malnutrition and contributes to the poor prognosis of patients on hemodialysis and chronic ambulatory peritoneal dialysis. Such a risk of survival may result not only from the malnutritional state, but also from unknown mechanisms resulting from parathyroid hormone (PTH) deficiency, or from other abnormalities that suppress PTH secretion. Another major abnormality underlying adynamic bone disease is the skeletal resistance to PTH in patients with uremia. Owing to the recent research on bone turnover at the molecular level, several new mechanisms for this abnormality have been elucidated. Correction of this ‘skeletal resistance to PTH’ will lead to the optimal management of parathyroid function and bone turnover in the future.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Metabolic acidosis induces calcium efflux from bone and in the process buffers the additional hydrogen ions. Initially metabolic acidosis stimulates physicochemical mineral dissolution and then cell-mediated bone resorption. Acidosis increases activity of the bone resorbing cells, the osteoclasts, and decreases activity of the bone forming cells, the osteoblasts. Osteoblastic immediate early response genes are inhibited as are genes controlling matrix formation.

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

摘要:

The identification ofPKD1andPKD2, the two major genes responsible for autosomal dominant polycystic kidney disease, are the seminal discoveries upon which much of the current investigation into the pathogenesis of this common heritable disease is based. A major mechanistic insight was achieved with the discovery that autosomal dominant polycystic kidney disease occurs by a two-hit mechanism requiring somatic inactivation of the normal allele in individual polarized epithelial cells. Most recent advances are focused on the function of the respective protein products, polycystin-1 and polycystin-2. Indirect evidence supports an interaction between polycystin-1 and -2, albeit it is unlikely that they work in concert in all tissues and at all times. They associate in yeast two hybrid and cotransfection assays and there is a striking similarity in the renal and pancreatic cystic phenotypes of Pkd2−/−and Pkd1del34/del34mice. Also, the respective homologues of both proteins are expressed in the same sensory neuronal cells in the nematode and the human disease phenotypes remain completely overlapping with the major difference being in relative severity. Mounting evidence supports the hypothesis that polycystin-1 is a cell surface receptor. A close homologue in the sea urchin sperm mediates the acrosome reaction in response to contact with egg-jelly, the nematode homologue functions in mechano- or chemosensation, and the solution structure of the repeated extracellular polycystic kidney disease domains reveals a β-sandwich fold commonly found in surface receptor molecules. Indirect evidence also supports the initial hypothesis that polycystin-2 is a calcium channel subunit. Several closely related homologues retain the calcium channel signature motif but differ in their predicted interaction domains, and one of these homologues has been shown to be a calcium regulated cation channel. Several important distinctions in polcystin-1 and -2 function have also been discovered. Polycystin-2 has a role in cardiac development that polcystin-1 does not. High level polycystin-2 expression in renal epithelial cells coincides with maturation and elongation of tubules and, unlike polycystin-1, persists into adulthood. In cells in tissue culture, polycystin-2 is expressed exclusively in the endoplasmic reticulum whilst the cellular expression of polycystin-1 remains unknown. Overall, the difficult task of understanding the autosomal dominant polycystic disease process is proceeding apace.

ISSN:1062-4821    

出版商:OVID    

年代:2000

数据来源: OVID