Maternal undernutrition and the offspring kidney: from fetal to adult life

Maternal dietary protein restriction during pregnancy is associated with low fetal birth weight and leads to renal morphological and physiological changes. Different mechanisms can contribute to this phenotype: exposure to fetal glucocorticoid, alterations in the components of the renin-angiotensin system, apoptosis, and DNA methylation. A low-protein diet during gestation decreases the activity of placental 11ß-hydroxysteroid dehydrogenase, exposing the fetus to glucocorticoids and resetting the hypothalamic-pituitary-adrenal axis in the offspring. The abnormal function/expression of type 1 (AT1R) or type 2 (AT2R) AngII receptors during any period of life may be the consequence or cause of renal adaptation. AT1R is up-regulated, compared with control, on the first day after birth of offspring born to low-protein diet mothers, but this protein appears to be down-regulated by 12 days of age and thereafter. In these offspring, AT2R expression differs from control at 1 day of age, but is also down-regulated thereafter, with low nephron numbers at all ages: from the fetal period, at the end of nephron formation, and during adulthood. However, during adulthood, the glomerular filtration rate is not altered, due to glomerulus and podocyte hypertrophy. Kidney tubule transporters are regulated by physiological mechanisms; Na+/K+-ATPase is inhibited by AngII and, in this model, the down-regulated AngII receptors fail to inhibit Na+/K+-ATPase, leading to increased Na+ reabsorption, contributing to the hypertensive status. We also considered the modulation of pro-apoptotic and anti-apoptotic factors during nephrogenesis, since organogenesis depends upon a tight balance between proliferation, differentiation and cell death.

Progress of zebrafish applied to kidney research / 国际儿科学杂志

As a kind of new model organisms,zebrafish attracts more and more scientists'attention.Because the nephrogenesis and much of kidney disease in zebrafish are similar to those in mammalian,many genes in both kidneys are conserved,and zebrafish has the more simple pronephron,which is convenient to operation and observation.The fish pronephron has been generally applied to study the development and disease of mammalian kidney.This review will focus on recent progress in applying the zebrafish pronephrons to issues of human health and development.

The Expression of Interleukin-6 and Its Receptor in the Developing Rat Kidney / 체질인류학회지

Interleukin-6 (IL-6) and its receptor are presumed to play important roles in the developing nervous system. However, little is known about their potential role(s) in the developing kidney. To investigate this, we have studied the expression of IL-6 and its receptor (IL-6R) in the developing rat kidney. Kidneys from 16- (F16), 18- and 20-day-old (F20) fetuses, 1- (P1), 3- (P3), 7- (P7) and 14-day-old (P14) pups, and adult rats were extracted. Renal expressions of IL-6 and its receptors were examined by immunohistochemistry and in situ hybridization respectively. Il-6 protein already appeared in F16. The early stage of renal development before birth, IL-6 showed strong immunoreactivity in the ureteric bud, metanephric mesenchymal cells (MMC) and developing glomerulus. The expression pattern of IL-6 in nephrogenic zone are very similar even after birth. In matured nephron after birth, IL-6 immunoreactivities were detected in distal tubules strongly, and collecting ducts moderately and thick ascending limb weekly. IL-6R hybridization signals have also already appeared in 16-day old fetal kidney. Before birth, IL-6R mRNAs were expressed in ureteric bud, MMC and developing glomerulus. In the matured nephron after birth, IL-6R mRNA was expressed in the thick ascending limb, distal tubules, collecting ducts and S3 segment of proximal tubule. These results suggest that IL-6 and its receptor may be involved in regulation of nephron formation in nephrogenic zone of rat, and play a role in distal nephron including collecting duct after birth.

Terapia celular en enfermedades renales y cardiovasculares / Cell therapy in renal and cardiovascular disease

Aunque se han logrado grandes avances en el campo de la biología molecular, todavía no se han esclarecido completamente los mecanismos responsables de la organogénesis y los factores que modulan el proceso de desarrollo, proliferación, crecimiento y maduración celulares durante la vida fetal y adulta. Los animales comparten la capacidad de regenerar tejidos y órganos, como un mecanismo biológico importante de defensa. En el caso del riñón, luego del daño tisular secundario a una noxa, se produce recuperación anatómica y funcional de la integridad, acompañada por la activación de un proceso sofisticado, mal comprendido, que lleva al reemplazo de las células tubulares dañadas por otras funcionalmente normales que reorganizan la arquitectura tubular. Este fenómeno de recambio se produce gracias a la presencia de células madre adultas somáticas exógenas, responsables del proceso de mantenimiento de la homeostasis renal, y posiblemente por células renales intrínsecas

Although there have been important advances in the field of molecular biology, the mechanisms responsible for nephrogenesis and the factors that modulate the process of development, proliferation, growth, and maturation during fetal and adult life have not been thoroughly explained. Animals, including mammals, share the intrinsic ability to regenerate tissues and organs as an important biological defense mechanism. In the case of the kidney, after tissue damage secondary to injury, anatomical and functional recovery of integrity is achieved, accompanied by the activation of a complex, poorly understood process, leading to the replacement of damaged tubular cells by functional ones that reorganize tubular architecture. This regeneration and repair process is produced by somatic, exogenous, adult stem cells, and probably by intrinsic renal stem cells, that are responsible for maintaining renal homeostasis

Expression of Nestin in the Developing Rat Kidney / 대한해부학회지

Nestin is abundantly expressed in stem cells of the developmental stage of both central nervous system and some non-neuronal organs. The aim of this study was to examine the expression of nestin in the developing rat kidney. Kidneys from 16-(F16), 18- and 20-day-old fetuses, 1-, 3-, 7-, 14-, and 21-day-old pups (P21) and adult were preserved and processed for immunohistochemistry. The nestin was already expressed at all areas of kidney from F16, especially strong in nephrogenic zone. Throughout the development, nestin immunoreactivity was exclusively localized in both glomerulus and interstitium, not in renal tubules. In the vesicle and the S-shaped body stages of the glomerulogenesis, nestin was negative. In the capillary loop stage, the immature podocytes became positive for nestin. Aggregated mesenchymal cells at the root of immature glomeruli were nestin-positive, and then lost the immunoreactivity progressively. In the maturing stage, nestin was expressed only in podocytes. In the renal interstitium except renal papilla, nestin was positive and colocalized with vimentin in almost all the interstitial cells at the prenatal age except both ED-1-positive macrophages and in MHC class II-positive dendritic cells. After birth, the number of nestin-positive cells in the interstitium was decreased, and at P21 pattern of nestin expression in the interstitium was similar with that of adult kidney. In the renal papilla, lipid-laden cells show nestin-negative but vimentin-positive.

Expression of Osteopontin in the Adult and Developing Rat Kidney / 대한해부학회지

Osteopontin (OPN), originally considered to be a bone protein, is now reported to be expressed in other tissues, notably in kidney. OPN has been demonstrated in the kidney by Northern and Western analyses, immunohistochemistry and in situ hybridization. However, studies of the cellular distribution of OPN in the kidney, especially in normal condition, have given highly conflicting results. This study is designed to establish the expression of OPN in kidney from the fetus to adult. Kidneys from 16-(F16), 18-(F18), and 20 day-old (F20) fetuses and 1-(P1), 3-(P3), 7-(P7), 14-(P14), 21 day-old pups, and adult were studied by in situ hybridization and immunohistochemistry. OPN mRNA and protein were expressed in the thick ascending limb (TAL) at F18 and F20, but disappeared gradually after birth. In the collection duct (CD), weak labeling appeared in a few cells at F20. After birth cells with strong labeling were scattered throughout the CD in the medulla and inner cortex at P1-P7 and in the outer cortex at P14. There was little OPN expression in the CD at P21. OPN mRNA and immunoreactivity appeared in the papillary surface epithelium (PSE) at F20 and in the descending thin limb (DTL) at P1. After birth OPN expression gradually increased to adult levels in the PSE. In the DTL, adult levels of expression were reached at P21. Proximal tubules exhibited a punctate subapical OPN immunos-taining from F18, but no hybridization signal. During renal development, the transient expression of OPN in the TAL and CD suggests that OPN may have a role in the developing kidney, and from P21 OPN expression was localized at DTL and PSE exclusively, which was similar to adult OPN expression pattern.