[Juxtaglomerular blood flow pathway in the kidney (comparative-anatomical and age-related aspects)].

To observe the formation of blood flow in the juxtaglomerular pathway in comparative-anatomical and age-related aspects, 484 kidneys from the representatives of the five classes of vertebrates, 50 kidneys of human fetuses and 193 kidneys of normal individuals of different ages were studied. Macro-microscopic, histological and morphometric methods were used. In all the mammalian animal species, the significant development of vascular glomeruli and peritubular capillaries was observed. In human kidneys, the relative content of cortical and medullary arterial vessels was maximal in juvenile age. With age, this parameter was found to decrease both in renal cortex and medulla. The differentiation of renal tissue into the cortex and the medulla, that began in birds and was finally formed in mammals, explains the appearance of cortical and juxtamedullary blood flow pathways. During the antenatal period of human development, renal juxtaglomerular pathway of blood flow prevails over the cortical one. The diminished significance of juxtamedullary pathway of blood flow in elderly and senile age determines the decreased adaptive capacities of intraorgan renal arterial bed in the norm.

Renin cells are precursors for multiple cell types that switch to the renin phenotype when homeostasis is threatened.

Renin-synthesizing cells are crucial in the regulation of blood pressure and fluid-electrolyte homeostasis. Adult mammals subjected to manipulations that threaten homeostasis increase circulating renin by increasing the number of renin-expressing/-releasing cells. We hypothesize that the ability of adult cells to synthesize renin does not occur randomly in any cell type, depending instead on the cell's lineage. To determine the fate of renin-expressing cells, we generated knockin mice expressing cre recombinase in renin-expressing cells and crossed them with reporter mice. Results show that renin-expressing cells are precursors for a variety of cells that differentiate into non-renin-expressing cells such as smooth-muscle, epithelial, mesangial, and extrarenal cells. In the kidney, these cells retain the capability to synthesize renin when additional hormone is required to reestablish homeostasis: specific subpopulations of apparently differentiated cells are "held in reserve" to respond (repeatedly) by de-differentiating and expressing renin in response to stress, and re-differentiating when the crisis passes.

TGF-beta type II receptor in rat renal vascular development: localization to juxtaglomerular cells.

To further define the role of transforming growth factor-beta (TGF-beta) receptors in renal vascular development, detailed immunohistochemical studies of TGF-beta receptor expression were performed from gestational day 15 through adulthood. On gestational day 15, TGF-beta type II receptor immunoreactivity was restricted to perirenal stromal and vascular cells. On gestational day 17 TGF-beta type II receptor immunoreactive stromal cells were observed within the kidney, with the same distribution as stromal alpha-smooth muscle actin and renin immunoreactive cells, and intense stromal TGF-beta type II receptor immunoreactivity continued through postnatal day 5. As vascular development progressed, TGF-beta type II receptor, alpha-smooth muscle actin and renin immunoreactivity became progressively restricted to small renal arteries and arterioles. Expression of TGF-beta type II receptors and renin was very intense in afferent glomerular arterioles during postnatal days 5 to 15, and then became progressively restricted only to juxtaglomerular cells in the mature kidney. TGF-beta type I receptor (ALK-5, ALK-1 and ALK-2) immunoreactivity was not detected in stromal or vascular elements during development or in the mature kidney. Intense TGF-beta type II receptor expression in renal stromal vascular smooth muscle cell precursors and developing blood vessels suggests a role for the TGF-beta type II receptors in the formation of the renal vascular smooth muscle compartment. The continued intense expression in juxtaglomerular cells argues for a role in renin synthesis and/or release. The absence of ALK-5, ALK-1, and ALK-2 in developing vascular smooth muscle and mature juxtaglomerular cells indicates that the canonical view of TGF-beta signaling may not hold in these locations.

Zis: a developmentally regulated gene expressed in juxtaglomerular cells.

Renal juxtaglomerular (JG) cells are specialized myoepithelioid cells located in the afferent arteriole at the entrance to the glomerulus. Their main function and distinctive feature is the synthesis and release of renin, the key hormone-enzyme of the renin-angiotensin system that regulates arterial blood pressure. Despite their relevance to health and disease, not much is known about factors that confer and/or maintain JG cell identity. To identify genes uniquely expressed in JG cells, we used a cell culture model and RNA differential display. JG cells cultured for 2 days express renin and renin mRNA, but after 10 days in culture they no longer contain or release renin and renin mRNA is reduced 700-fold. We report one cDNA differentially expressed in the 2-day JG cell culture that detects a 2.6-kb mRNA expressed at higher levels in newborn than adult kidney. Screening a 2-day culture JG cell cDNA library yielded clones representing differentially spliced transcripts. These cDNAs encode one unique protein (Zis) containing zinc fingers and domains characteristic of splicing factors and RNA binding proteins. Northern blot analysis confirmed Zis mRNA expression in differentiated JG cells, and identified an additional unique 1.5-kb transcript. The Zis transcripts are developmentally regulated in kidney and a number of other organs. The features of the Zis protein and its organ distribution suggest a possible role in regulation of transcription and/or splicing, both important steps for controlling developmentally expressed genes.

Ontogeny of NO synthase and renin in juxtaglomerular apparatus of rat kidneys.

The presence of NO synthase (NOS) in cells of the macula densa (MD) suggests a role for arginine-derived NO in tubulovascular information transfer. To investigate the postnatal development of the neuronal isoform of NOS and of renin in the kidney, the cellular distribution of these enzymes was examined in perfusion-fixed kidneys of 2-, 6-, and 15-day-old rats at both the protein and mRNA level (n = 4 rats/group). NOS and renin and their mRNAs were localized by immunohistochemical and in situ hybridization methods. In addition, NOS levels were assessed by using NADPH diaphorase (NADPH-d) histochemistry. For quantification, the fraction of NOS- and renin-positive glomeruli as well as the number of NOS-positive MD cells was evaluated at all stages. Presence of NOS in single cells of the developing distal tubule was encountered already in the S-shaped body. Full expression of a NOS signal in MD cells was seen as soon as a glomerular urinary space was developed. Double labeling with NADPH-d and antibody to Tamm-Horsfall protein (THP) indicated mutual exclusiveness of NADPH-d-positive MD cells and neighboring THP-positive distal tubule cells at all levels of development. The relative intensity of renin status was 2 day > 6 day > 15 day, whereas NOS expression was maximal on postnatal day 6. Our data are consistent with an involvement of MD NO synthesis in the early organization of the juxtaglomerular apparatus during nephrogenesis and suggest an interdependent relation with renin-producing cells.

Structural and functional development of outer versus inner cortical proximal tubules.

The concept of centrifugal renal development is based on renal embryogenesis. It implies a relationship between nephron age and nephron position along a cortical to medullary axis. In common usage, however, it often also implies a relationship between nephron age or position and nephron maturity. We consider here whether the ideas of centrifugal development and centrifugal maturation should in fact be considered as separate and distinct concepts. That is, we consider the possibility that nephron maturity does not necessarily correlate with nephron age. Unfortunately, pertinent reported data give no clear answer. We conclude only that further study will be required before definitive conclusions about renal developmental stages can be stated with certainty.

[Effects of castration on the development of the juxtaglomerular apparatus in the albino rat during growth]. / Effets de la castration sur le développement de l'appareil juxtaglomérulaire du rat albinos pendant la période de croissance.

With the purpose to show a possible sexual difference in the evolution of the juxtaglomerular granular cells during the albino rat post-natal development, the authors have compared groups of male and female animals of crescent ages from 2 to 90 days old. During the first 30 days, the granulation indexes, which express the secretory activity of the Ruyter cells, are regularly increasing as the body and renal weights. On and after the 30th day, the growth becomes more important for males than for females but, in spite of these weight differences, the granulation indexes are not significantly different in terms of sex, at the same age. In order to control these results, castrations have been performed during the period of granular cells increase, on the 17th day of life. The comparison of castrated and uncastrated animals on the 35th day shows that castration causes repercussions on the body and renal growth. On the other hand, no significant modification of the granulation indexes occurs, which brings the demonstration that the Ruyter cells development is independent of the animal sex.

Evolution of the granular cells of the juxtaglomerular apparatus during postnatal development in the albino rat. Effect of age, body weight, renal weight and sex.

The postnatal development of the juxtaglomerular apparatus was studied by fluorescent microscopy in a series of 275 albino Wistar rats aged from 2 to 90 days. After treatment of kidney sections with thioflavine T, the appearance and evolution of secretory function in the terminal segment of the afferent glomerular arteriole were assessed in terms of the granular cell index (GCI) and the juxtaglomerular cell granulation index (JGI). Variations in these indices were analyzed in function of age, body weight, renal weight and sex of the animals. It emerges quite clearly from these studies that granular cell differentiation and maturation takes place in four successive stages: (a) a growth and differentiation phase lasting from the 2nd day to the beginning of the 5th week of extra-uterine life; (b) a critical phase around day 30; (c) a declining phase from day 30 to day 45, and (d) a stabilization phase from day 45 onwards. Until day 30 this evolutionary pattern is paralleled by rising body weight in animals of both sexes; afterwards it becomes independent of the parameters studied, in the males as well as in the females. The pattern of kidney weight parallels that of growth in body size and weight and does not constitute a more specific variable than body weight in the study of the developing granules in the juxtaglomerular apparatus.

Postnatal development of the kidney juxtaglomerular apparatus in rats.

The development of the juxtaglomerular (JG) apparatus in the rat kidney was investigated at different times of postnatal life (1, 2, 3, 5, 7, 10, 15, 30 and 60 days). On the 1st day after birth, secretory granules were found in JG cells in preglomerular arterioles of juxtamedular nephrons and in interglobular arteries. JG indices are high at this stage and decrease until the 5th day, then gradually rise until the 60th day. The possible reasons for such findings are discussed. Macula densa cells start to differ as early as the 1st day after birth. They are very distinct already at 2 days and they reach typical organization by the 15th day. Extraglomerular mesangial cells are few in early postnatal life. Their number increases later on. The parallelism between nephrogenesis and development is discussed.