SEARCH · PubMed Health

Results for “renal development”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed1997

Angiotensin's role in renal development.

All the components of the renin-angiotensin system (RAS) are highly expressed in the developing kidney in a unique spatial and temporal pattern that is associated with nephrogenesis, vascularization, and the proper architectural and functional development of this organ. Pharmacological inhibition of the RAS results in structural and functional developmental abnormalities of the kidneys in several animal species, including humans. Similarly, altered renal morphology and functional abnormalities have been described in mice with targeted inactivation of the angiotensinogen (Agt) and the angiotensin-converting enzyme (ACE) genes. In contrast, inactivation of angiotensin receptors have not resulted in renal morphological abnormalities, suggesting a redundancy at this level of the RAS cascade that prevents the development of renal pathology. More importantly, inactivation of the ACE or Ao genes results in a renal phenotype remarkably similar to that obtained with pharmacological inhibition of the RAS. Taken together, the available information suggests that angiotensin is necessary for normal kidney development and for the maintenance of the functional and structural integrity of the adult kidney.

Adult↗

PubMed2006

Differential expression of the intermediate filament protein nestin during renal development and its localization in adult podocytes.

Nestin, an intermediate filament protein, is widely used as stem cell marker. Nestin has been shown to interact with other cytoskeleton proteins, suggesting a role in regulating cellular cytoskeletal structure. These studies examined renal nestin localization and developmental expression in mice. In developing kidney, anti-nestin antibody revealed strong immunoreactivity in vascular cleft of the S-shaped body and vascular tuft of capillary loop-stage glomerulus. The nestin-positive structures also were labeled by endothelial cell markers FLK1 and CD31 in immature glomeruli. Nestin was not detected in epithelial cells of immature glomeruli. In contrast, in mature glomerular, nestin immunoreactivity was observed only outside laminin-positive glomerular basement membrane, and co-localized with nephrin, consistent with podocyte nestin expression. In adult kidney, podocytes were the only cells that exhibited persistent nestin expression. Nestin was not detected in ureteric bud and its derivatives throughout renal development. Cell lineage studies, using a nestin promoter-driven Cre mouse and a ROSA26 reporter mouse, showed a strong beta-galactosidase activity in intermediate mesoderm in an embryonic day 10 embryo and all of the structures except those that were derived from ureteric bud in embryonic kidney through adult kidney. These studies show that nestin is expressed in progenitors of glomerular endothelial cells and renal progenitors that are derived from metanephric mesenchyme. In the adult kidney, nestin expression is restricted to differentiated podocytes, suggesting that nestin could play an important role in maintaining the structural integrity of the podocytes.

Aging↗

PubMed2004

Stent-graft placement combined with percutaneous fenestration for the treatment of aortic dissection in a patient at risk of developing renal ischemia.

A 51-year-old man, suffering from an aortic dissection with the entry tear in the descending thoracic aorta, underwent replacement of the ascending aorta and aortic arch with resection of the entry tear. Although the false lumen of the descending thoracic aorta was thrombosed after surgery, redissection developed in the descending aorta 2 months later. Percutaneous fenestration was performed before stent-grafting because it was judged that there was a significant risk of left renal ischemia. Entry closure with a stent-graft was performed successfully and no renal ischemia developed. The patient is doing well at 1 year after the procedure.

Anastomosis, Surgical↗

PubMed2006

Maternal nutrient restriction alters renal development and blood pressure regulation of the offspring.

Studies have shown that the risk of hypertension in adulthood can be affected by the in utero environment. It is established that hypertension is linked to compromised kidney function and that factors affecting organogenesis can increase the risk of later disease. Prostaglandins (PG) and growth factors are known to play an important role in regulating kidney function and renal organogenesis. The extent, however, to which global energy restriction (where all nutrients are reduced) of the mother can programme later blood pressure control or renal PG and growth factor status is unknown. A study is described that aimed to examine the long-term effects of maternal nutrient restriction (NR) and elucidate their relationship with compromised kidney development. First, it was necessary to establish animal models. A sheep model of 50% NR during specific stages of gestation was used to investigate fetal renal development, whilst a rat model of 50% NR throughout pregnancy was used to investigate postnatal kidney development and adult functioning. Molecular analysis has shown that expression of the growth hormone-insulin-like growth factor (GH-IGF) axis is affected by NR in the fetal sheep kidneys, and that changes are dependent on the timing of NR and whether the fetus is a singleton or a twin. Analysis of the kidneys from the rat model has shown nutritional differences in the expression of PG receptors and the enzymes responsible for PG synthesis and degradation that persist into adulthood. In conclusion, NR does affect the GH-IGF and PG axes, and these changes may be important in the nutritional programming of renal functioning and adult blood pressure control.

Animals↗

PubMed2006

Sex differences in postnatal growth and renal development in offspring of rabbit mothers with chronic secondary hypertension.

Previously, we demonstrated that adult blood pressure was increased in offspring of rabbit mothers with chronic secondary renal hypertension. Our study identified sex-specific differences in the programming of hypertension, with female, not male, offspring, having increased blood pressure at 30 wk of age. The aim of this study was to characterize the maternal hypertension during pregnancy to determine potential programming stimuli. Further, we examined the impact of chronic maternal hypertension on offspring birth weight, nephron number, and renal noradrenaline content (as an index of renal innervation density). Three groups of mothers and their offspring were studied: two-kidney, one-wrap (2K-1W, n = 9 mothers) hypertensive, two-kidney, two-wrap (2K-2W, n = 8) hypertensive, and a sham-operated group (n = 9). Mean arterial blood pressure was increased by approximately 20 mmHg throughout pregnancy in both hypertensive groups compared with sham mothers (P(G) < 0.001). Plasma renin activity (PRA; P(G) < 0.05) and aldosterone (P(G) < 0.05) levels were increased during gestation in the 2K-1W, but not the 2K-2W mothers. Birth weight was increased by approximately 20% in offspring of both groups of hypertensive mothers (P(T) < 0.001), though this was associated with a reduction in litter size. Renal noradrenaline content was increased ( approximately 40%, P < 0.05) at 5 wk of age in female 2K-1W offspring compared with sham offspring. Glomerular number was not reduced in female offspring of either group of hypertensive mothers; however, glomerular tuft volume was reduced in female 2K-2W offspring (P < 0.05), indicative of a reduction in glomerular filtration surface area. In conclusion, the two models of renal hypertension produced differential effects on the offspring. The impact of a stimulated maternal renin-angiotensin system in the 2K-1W model of hypertension may influence development of the renal sympathetic nerves and contribute to programming of adult hypertension.

Aldosterone↗

PubMed1995

Basic fibroblast growth factor can mediate the early inductive events in renal development.

The earliest characterized events during induction of tubulogenesis in renal anlage include the condensation or compaction of metanephrogenic mesenchyme with the concurrent upregulation of WT1, the gene encoding the Wilms tumor transcriptional activator/suppressor. We report that basic fibroblast growth factor (FGF2) can mimic the early effects of an inductor tissue by promoting the condensation of mesenchyme and inhibiting the tissue degeneration associated with the absence of an inductor tissue. By in situ hybridization, FGF2 was also found to mediate the transcriptional activation of WT1 and of the hepatocyte growth factor receptor gene, c-met. Although FGF2 can induce these early events of renal tubulogenesis, it cannot promote the epithelial conversion associated with tubule formation in metanephrogenic mesenchyme. For this, an undefined factor(s) from pituitary extract in combination with FGF2 can cause tubule formation in uninduced mesenchyme. These findings support the concept that induction in kidney is a multiphasic process that is mediated by more than a single comprehensive inductive factor and that soluble molecules can mimic these inductive activities in isolated uninduced metanephrogenic mesenchyme.

Animals↗

PubMedDate not supplied

Retinoids and renal development.

Although it has long been appreciated that retinoids play an essential role in kidney organogenesis, it has only recently been recognized that even mild fetal vitamin A deficiency syndromes can result in a reduction in nephron number. Recent studies have also begun to define the cellular and molecular events associated with retinoid actions in the fetal kidney and have demonstrated the essential function of retinoids in branching growth of the ureteric bud. Importantly, characterization of the renal developmental effects of RAR alpha/beta 2 double homozygous mice combined with metanephric organ culture studies have together shown that one essential function of retinoid action in the developing kidney is the maintenance of c-ret expression in the tips of the ureteric bud. However, many other potential retinoid target genes including midkine, sonic hedgehog, Hox d-11, matrix metalloproteinases, and tissue inhibitors of metalloproteinases appear to play important roles in renal development and might be important downstream mediators of retinoid effects in the developing kidney. It can, therefore, be anticipated that important new insights into fetal kidney development will be forthcoming in the near future, as the essential target genes affected by retinoid signal transduction are progressively elucidated.

Animals↗

PubMed1995

Transcription factors in renal development: the WT1 and Pax-2 story.

The development of a complex, multicellular organ, such as the kidney, from two embryonic progenitor tissues requires the activation and suppression of transcription factors that regulate tissue and cell type-specific gene expression. From areas as diverse as fruit fly development and human cancer genetics, a number of important genes have been identified that help to orchestrate the early events of renal epithelium induction and differentiation. The Wilms' tumor-suppressor gene WT1 is critical for regulating the early response of the kidney mesenchyme to induction and may play multiple roles during the course of renal epithelial cell development and tumor formation. The Pax-2 gene is activated in the mesenchyme after induction and is necessary for condensation and perhaps proliferation of the induced cells. How these two important gene products exert their effects will be discussed in light of recent evidence on DNA binding, transcription repression, and protein interactions.

Animals↗

PubMed1994

Developing renal microvasculature can be maintained under perfusion culture conditions.

The cortex corticis of the neonatal rabbit kidney consists of developing nephrons, vessels, collecting duct ampullae and the nephrogenic mesenchyme. Inductive interactions between embryonic mesenchyme and collecting duct ampullae lead to the coordinated development of the nephrons and the collecting duct system. The factors regulating nephrogenesis and vascular development within this tissue region are unknown. In order to analyze the hormonal regulation of vascular development an organotypic culture system was established. Cortex explants from neonatal rabbit kidneys were prepared, mounted in a set of holding rings and cultured under serum-free conditions for 14 days in conventional culture plates or under permanent medium perfusion in a newly developed culture container. The detection of endothelial cells was carried out by means of two monoclonal antibodies. Within the renal cortex corticis EnPo 1 detected developing vasculature as well as podocytes and a subset of mesenchymal cells. EC1 displayed exclusive specificity for endothelial cells. The antibody did not discriminate between arteries and veins. Endothelial cells of different developmental stages were labeled with the same intensity. A combination of both antibodies allowed the discrimination between developing endothelial cells and podocytes. Following 14 days of culture under permanent medium exchange, excellent tissue preservation as well as endothelial cell proliferation was observed in cortex explants. In contrast, tissue kept in stationary culture revealed a high degree of disintegration. Endothelial antigen expression was also severely disturbed. Tissue maintenance under stationary conditions was improved by the application of a hormone mixture consisting of aldosterone and 1,25-hydroxyvitamin D3. However, the high degree of spatial organization shown by developing endothelial cells in vivo was maintained exclusively in explants cultured in the presence of hormone under permanent perfusion.

Aldosterone↗

PubMed1997

Roles of growth factors in renal development.

The branching of the ureteric bud and the differentiation of renal mesenchyme into nephrons are interdependent processes. Experiments with organ culture and genetically engineered mice suggest that metanephric growth factors regulate these events. Renal mesenchyme produces glial cell line-derived neurotrophic factor, an essential molecule for ureteric bud growth, whereas multiple growth factors are required for nephron formation: these include fibroblast growth factor 2, Wnt4 and bone morphogenetic protein 7. Deregulation of growth factors may be implicated in the pathogenesis of congenital kidney malformations.

Animals↗

PubMed1997

Ontogeny of the intrarenal kallikrein-kinin system: proposed role in renal development.

The kallikrein-kinin system (KKS) plays an important role in the regulation of renal function. Endogenous kinins modulate renal microvascular resistance, medullary blood flow, and distal nephron sodium and water reabsorption. All the components of the KKS, including tissue kallikrein, kininogen, kininase II, and kinin receptors are expressed within the kidney, establishing a paracrine system capable of controlling local nephron functions. In this review, data will be presented demonstrating that the developing kidney expresses an endogenous, functionally active KKS. Molecular studies have shown that gene expression of the renal KKS in the rat is activated postnatally, and that the intrarenal distribution of KKS components is subject to developmental control. Furthermore, the developmental expression of KKS appears to be regulated primarily at the transcriptional level. Ontogenetic studies have also revealed that the bradykinin B-2 receptor gene is overexpressed in the developing rat kidney. As kinins are potent vasoactive and growth-promoting factors, it is proposed that endogenous kinins mediate developmental renal growth and differentiation, and modulate the maturational changes which occur in renal hemodynamics.

Amino Acid Sequence↗

PubMed1999

Tubulointerstitial nephritis antigen: an extracellular matrix protein that selectively regulates tubulogenesis vs. glomerulogenesis during mammalian renal development.

Tubulointerstitial nephritis antigen (TIN-ag) is an extracellular matrix protein and is expressed in the renal tubular basement membranes. Its role in metanephric development was investigated. TIN-ag cDNA, isolated from the newborn mouse library, had an ORF of 1,425 nucleotides, a putative signal sequence, and an ATP/GTP-binding site. The translated sequence had approximately 80% identity with rabbit TIN-ag. Among various tissues, TIN-ag mRNA was primarily expressed in the newborn kidney. In the embryonic metanephros, TIN-ag expression was confined to the distal convolution or pole of the S-shaped body, the segment of the nascent nephron that is the progenitor of renal tubules. Treatment with TIN-ag antisense oligodeoxynucleotide induced dysmorphogenesis of the embryonic metanephroi, malformation of the S-shaped body, and a decrease in the tubular population, whereas the glomeruli were unaffected. Treatment also led to a decrease of TIN-Ag mRNA, de novo synthesis of TIN-ag protein, and its antibody reactivity. The mRNA expression of glomerular epithelial protein 1 (a marker for renal podocytes), anti-heparan-sulfate-proteoglycan antibody reactivity, and wheat germ agglutinin lectin staining of the metanephros were unaffected. The anti-TIN-ag antibody treatment also caused deformation of the S-shaped body and a reduction in the tubular population, whereas the glomeruli were unchanged. The data suggest that the TIN-ag, unlike other basement membrane proteins, selectively regulates tubulogenesis, whereas glomerulogenesis is largely unaffected.

Amino Acid Sequence↗

PubMed1998

An endothelial growth factor involved in rat renal development.

In the kidney, there is a close and intricate association between epithelial and endothelial cells, suggesting that a complex reciprocal interaction may exist between these two cell types during renal ontogeny. Thus, we examined whether metanephrogenic mesenchymal cells secrete endothelial mitogens. With an endothelial mitogenic assay and sequential chromatography of the proteins in the media conditioned by a cell line of rat metanephrogenic mesenchymal cells (7.1.1 cells), we isolated a protein whose amino acid analysis identified it as hepatoma-derived growth factor (HDGF). Media conditioned with Cos-7 cell transfected with HDGF cDNA stimulated endothelial DNA synthesis. With immunoaffinity purified antipeptide antibodies, we found that HDGF was widely distributed in the renal anlage at early stages of development but soon concentrated at sites of active morphogenesis and, except for some renal tubules, disappeared from the adult kidney. From a 7.1.1 cells cDNA library, a clone of most of the translatable region of HDGF was obtained and used to synthesize digoxigenin-labeled riboprobes. In situ hybridization showed that during kidney development mRNA for HDGF was most abundant at sites of nephron morphogenesis and in ureteric bud cells while in the adult kidney transcripts disappeared except for a small population of distal tubules. Thus, HDGF is an endothelial mitogen that is present in embryonic kidney, and its expression is synchronous with nephrogenesis.

Amino Acid Sequence↗

PubMed1998

Regulation of cell survival during renal development.

Apoptosis occurs in an orchestrated fashion during kidney development. In contrast, it is a relatively rare event in normal developed (adult) kidney. However, a predictable pattern of apoptosis is observed in adult kidney in two settings, during which parts of the developmental pattern are recapitulated. These are regeneration following acute ischemic injury and the process of cystogenesis in polycystic kidney disease. Apoptosis in kidney is regulated by agents both intrinsic and extrinsic to the renal cell. The protooncogene b-cell lymphoma/leukemia gene product-2 (bcl-2) is an important intrinsic factor. The growth factor epidermal growth factor is an important extrinsic regulator. A thorough understanding of the control of renal apoptosis during development and recovery from ischemic injury and in cystogenesis may lead to new therapies to prevent or ameliorate abnormalities of kidney formation, to enhance regeneration following acute ischemic injury, and to slow the progression of renal failure in polycystic kidney disease.

Animals↗

PubMed1986

Pharmacologic probing of renal development in the neonatal rat.

This study was designed to examine the ontogeny of renal functions in the neonatal rat using various pharmacologic agents as probes. The renal responses of 2-, 6-, and 10-day-old rats to diuretic agents known to act on proximal tubules, loops of Henle and distal tubules were assessed. These included acetazolamide, furosemide, mercaptomerin, chlorothiazide and amiloride. Following administration of a diuretic agent, urine was collected at 90-min intervals for 6 h and urine volume, osmolality, chloride and pH were measured. Acetazolamide, furosemide, chlorothiazide and amiloride induced diuresis at each age indicating that the respective reabsorptive mechanisms were present and functional by 2 days of age. At all ages furosemide evoked a maximal response in eliminating the interstitial fluid gradient as indicated by the formation of an isosmotic urine in treated pups. However, the volume of the diuresis at 2 days of age was half those at 6 and 10 days, reflecting enhanced activity of the countercurrent multiplication apparatus in the maturing pups. Administration of mercaptomerin did not produce pharmacologic diuresis, but rather resulted in acute renal failure; although the nephrotoxicity was to a lesser extent in 2-day-old pups. The ability of the neonatal rat to respond to these pharmacologic probes demonstrates that the integrity of these renal functions is established in this species early in postnatal life.

Acetazolamide↗

PubMed1996

Deregulation of cell survival in cystic and dysplastic renal development.

Various aberrations of cell biology have been reported in polycystic kidney diseases and in cystic renal dysplasias. A common theme in these disorders is failure of maturation of renal cells which superficially resemble embryonic tissue. Apoptosis is a feature of normal murine nephrogenesis, where it has been implicated in morphogenesis, and fulminant apoptosis occurs in the small, cystic kidneys which develop in mice with null mutations of bcl-2. Therefore, we examined the location and extent of apoptosis in pre- and postnatal samples of human polycystic and dysplastic kidney diseases using propidium iodide staining, in situ end-labeling and electron microscopy. In dysplastic kidneys cell death was prominent in undifferentiated cells around dysplastic tubules and was occasionally found in cystic epithelia. The incidence of apoptosis was significantly greater than in normal controls of comparable age both pre- and postnatally. In the polycystic kidneys there was widespread apoptosis in the interstitium around undilated tubules distant from cysts, in undilated tubules between cysts and in cystic epithelia. The level of apoptosis compared to controls was significantly increased postnatally. A similar increase of cell death was also noted in the early and late stages of renal disease in the polycystic cpk/cpk mouse model. We speculate that deregulation of cell survival in these kidneys may reflect incomplete tissue maturation, and may contribute to the progressive destruction of functional kidney tissue in polycystic kidneys and the spontaneous involution reported in cystic dysplastic kidneys.

Animals↗

PubMed1985

Do Nigerian diabetics with haemoglobin genotype Hb AS have greater risks of developing renal complications and hypertension? A preliminary report.

Thirty nine non-insulin dependent Nigerian diabetics (21 males and 18 females) aged 40-63 years (mean 50.6 years) with haemoglobin genotype Hb AA who had diabetes for 5-8 years were matched with an equal number of non-insulin dependent diabetics with haemoglobin genotype Hb AS for sex, age, duration of diabetes and state of control of diabetes. The occurrence of proteinuria and hypertension was studied in all patients; serum creatinine and 24 hour urine protein excretion were measured in those with proteinuria. Eight of the 39 diabetics with Hb AS had developed significant proteinuria compared to two with Hb AA (p less than 0.05). The serum creatinine was constantly above 2.0 mg/100 ml in four of the eight diabetics with Hb AS compared to one with Hb AA, whilst the 24 hour protein excretion in the urine was above 2.0 g in three diabetics with Hb AS compared to none with Hb AA. Twelve diabetics with Hb AS had hypertension compared to three with Hb AA (p less than 0.01). These results suggest that Nigerian diabetics with haemoglobin genotype Hb AS may have greater risks of developing proteinuria, with renal dysfunction and/or hypertension and probably diabetic nephropathy than their counterpart with haemoglobin genotype Hb AA.

Adult↗

PubMed1984

De novo cellular synthesis of sulfated proteoglycans of the developing renal glomerulus in vivo.

The site of cellular synthesis of glomerular proteoglycans was investigated in developing glomeruli of 4- to 5-day-old rats. [35S]Sulfate was administered intravenously and animals were sacrificed 15 min to 12 hr later. The outermost layers of the kidney cortices were utilized for characterization of proteoglycans and electron microscopic autoradiography. Sepharose CL-6B chromatography and cellulose acetate electrophoresis revealed that most (approximately equal to 96%) of the radioactivity was associated with heparan sulfate-proteoglycan synthesized during maturation of glomerular capillaries. Tissue autoradiography revealed the following: (i) during the S-shaped body stage, there is rapid incorporation of [35S]sulfate by mesenchymal cells into the cleft region (site for development of future glomerular extracellular matrices); (ii) during the precapillary stage, mesenchyme-derived cells showed higher incorporation of radioisotope than did epithelial cells; and (iii) during the mature capillary stage, all glomerular cell types (mesangial, endothelial, and epithelial) incorporated [35S]sulfate, incorporation by mesangial cells being the greatest. Radiolabeling was also higher in the mesangial matrix than in the glomerular basement membrane of peripheral capillary loops. Synthesis of a single major species of sulfated glycosaminoglycan by cells of different embryologic origin may be unique to glomerular capillaries.

Animals↗