scholarly journals State of the Art on Kidney Development: How Nephron Endowment at Birth Can Shape Our Susceptibility to Renal Dysfunction Later in Life

2019 ◽  
Vol 36 (S 02) ◽  
pp. S33-S36 ◽  
Author(s):  
Vassilios Fanos ◽  
Clara Gerosa ◽  
Cristina Loddo ◽  
Gavino Faa
Keyword(s):  
Birth Weight ◽  
Fetal Programming ◽  
Low Birthweight ◽  
Kidney Development ◽  
State Of The Art ◽  
Kidney Diseases ◽  
Nephron Endowment ◽  
Adult Kidney ◽  
Maternal Status

AbstractIn the present article, we discuss the following topics: (1) the fetal programming of adult kidney diseases and (2) the role of neonatologists in the regenerative renal medicine, based on the activation of resident renal SC. Here, we report the most important steps of our collaboration between neonatologists, nephrologists, and pathologists. Nephrologists should be more interested in clinical data regarding the first month of life in the womb of their adult patients, being particularly focused on birth weight and on the weeks of gestation at birth, without forgetting data regarding maternal status during gestation and neonatal asphyxia. Neonatologists should be aware that any preterm or low birthweight infant should be considered as a subject with fewer glomeruli, probably predicted to develop renal disease later in life.

scholarly journals Wnt signaling in kidney: the initiator or terminator?

2020 ◽  
Vol 98 (11) ◽  
pp. 1511-1523 ◽  
Author(s):  
Ping Meng ◽  
Mingsheng Zhu ◽  
Xian Ling ◽  
Lili Zhou
Keyword(s):  
Cell Differentiation ◽  
Embryonic Development ◽  
Wnt Signaling ◽  
Tissue Repair ◽  
Progenitor Cell ◽  
Kidney Development ◽  
Kidney Diseases ◽  
Electrolyte Balance ◽  
Tissue Repair And Regeneration

Abstract The kidney is a key organ in the human body that excretes toxins and sustains the water–electrolyte balance. During embryonic development and disease progression, the kidney undergoes enormous changes in macrostructure, accompanied by a variety of microstructural histological changes, such as glomerular formation and sclerosis, tubule elongation and atrophy, interstitial establishment, and fibrosis progression. All of these rely on the frequent occurrence of cell death and growth. Notably, to overcome disease, some cells regenerate through self-repair or progenitor cell differentiation. However, the signaling mechanisms underlying kidney development and regeneration have not been elucidated. Recently, Wnt signaling has been noted to play an important role. Although it is a well-known developmental signal, the role of Wnt signaling in kidney development and regeneration is not well recognized. In this review, we review the role of Wnt signaling in kidney embryonic development, tissue repair, cell division, and progenitor cell differentiation after injury. Moreover, we briefly highlight advances in our understanding of the pathogenic mechanisms of Wnt signaling in mediating cellular senescence in kidney parenchymal and stem cells, an irreversible arrest of cell proliferation blocking tissue repair and regeneration. We also highlight the therapeutic targets of Wnt signaling in kidney diseases and provide important clues for clinical strategies.

The role of folic acid in fetal programming of birth phenotypes and early human development: a biopsychosocial perspective

2013 ◽  
Vol 4 (6) ◽  
pp. 442-457 ◽  
Author(s):  
H. M. Salihu ◽  
A. Salinas-Miranda ◽  
C. de la Cruz ◽  
A. P. Alio
Keyword(s):  
Folic Acid ◽  
Fetal Programming ◽  
Low Birthweight ◽  
Population Based ◽  
Intrauterine Growth ◽  
Early Human Development ◽  
Potential Population ◽  
Biopsychosocial Perspective ◽  
Early Human

Preterm birth, low birthweight, intrauterine growth retardation and small for gestational age are birth phenotypes that significantly contribute to life-long morbidity and mortality. This review examines the epidemiologic and biologic evidence of folic acid (FA) as a potential population-based intervention to curtail some adverse birth phenotypic expressions, and by extension, their later physical and neurodevelopmental consequences. We outlined a feto-placental adaptation categorization taking into account how prenatal insults may be encoded in fetal development, the adaptive success of the feto-placental response, and subsequent expression in the health of the fetus. Although there are plausible biological pathways that can be implicated, we found that the epidemiological evidence on the role of perinatal FA nutriture and fetal programming of adverse birth phenotypes is still inconclusive. Because biologic and epidemiological considerations alone do not suffice in deciphering the utility of FA in averting adverse birth phenotypes, we proposed a biopsychosocial model that takes into account multi-layered psychosocial contexts for improving subsequent research studies in this area.

scholarly journals Mechanisms of Fetal Programming in Hypertension

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
John Edward Jones ◽  
Julie A. Jurgens ◽  
Sarah A. Evans ◽  
Riley C. Ennis ◽  
Van Anthony M. Villar ◽  
...  
Keyword(s):  
Birth Weight ◽  
Fetal Programming ◽  
Intrauterine Growth Restriction ◽  
Intrauterine Growth ◽  
Fetal Survival ◽  
Nephron Endowment ◽  
Developmental Program ◽  
Expression Of Genes ◽  
Underlying Mechanisms

Events that occur in the early fetal environment have been linked to long-term health and lifespan consequences in the adult. Intrauterine growth restriction (IUGR), which may occur as a result of nutrient insufficiency, exposure to hormones, or disruptions in placental structure or function, may induce the fetus to alter its developmental program in order to adapt to the new conditions. IUGR may result in a decrease in the expression of genes that are responsible for nephrogenesis as nutrients are rerouted to the development of more essential organs. Fetal survival under these conditions often results in low birth weight and a deficit in nephron endowment, which are associated with hypertension in adults. Interestingly, male IUGR offspring appear to be more severely affected than females, suggesting that sex hormones may be involved. The processes of fetal programming of hypertension are complex, and we are only beginning to understand the underlying mechanisms.

scholarly journals The role of endothelial glycocalyx in health and disease

2019 ◽  
Vol 12 (5) ◽  
pp. 611-619 ◽  
Author(s):  
Onur Yilmaz ◽  
Baris Afsar ◽  
Alberto Ortiz ◽  
Mehmet Kanbay
Keyword(s):  
State Of The Art ◽  
Kidney Diseases ◽  
Structure And Function ◽  
The Body ◽  
Endothelial Glycocalyx ◽  
Surrogate Markers ◽  
Disease States ◽  
Health And Disease ◽  
And Function

AbstractThe endothelium is the largest organ in the body and recent studies have shown that the endothelial glycocalyx (eGCX) plays a major role in health and disease states. The integrity of eGCX is vital for homoeostasis and disruption of its structure and function plays a major role in several pathologic conditions. An increased understanding of the numerous pathophysiological roles of eGCX may lead to the development of potential surrogate markers for endothelial injury or novel therapeutic targets. This review provides a state-of-the-art update on the structure and function of the eGCX, emphasizing the current understanding of interorgan crosstalk between the eGCX and other organs that might also contribute to the pathogenesis of kidney diseases.

scholarly journals Temporal Expression and Cellular Localization of PAPPA2 in the Developing Kidney of Rat

2020 ◽  
Vol 68 (3) ◽  
pp. 209-222
Author(s):  
Vikash Kumar ◽  
Chun Yang ◽  
Allen W. Cowley
Keyword(s):  
Mrna Expression ◽  
Cellular Localization ◽  
Kidney Development ◽  
Rat Kidney ◽  
Postnatal Growth ◽  
Brown Norway ◽  
Adult Kidney ◽  
Developing Kidney ◽  
P Rat

PAPPA2 is a metalloproteinase which cleaves insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5, and its role in pregnancy and postnatal growth is primarily studied. Using exclusion mapping, we reported a subcongenic (26-P) rat where a 0.71-Mbp region containing the pregnancy-associated plasma protein a2 ( Pappa2) allele of salt-insensitive Brown Norway (BN) was introgressed into Dahl saltsensitive (SS) genetic background, resulting in the reduction of salt sensitivity. Pappa2 was differentially expressed in the adult kidney of 26-P and SS rats. Here, the expression and cellular localization of Pappa2 in embryonic and postnatal kidneys of 26-P and SS rats were examined. Pappa2 mRNA expression was 5-fold higher in the embryonic kidney (day 20.5) of the 26-P rat compared with the SS rat. Pappa2 mRNA expression progressively increased with the development of kidney, reaching a peak at postnatal day 5 before trending downward in subsequent stages of development in both strains. At all tested time points, Pappa2 remained higher in the 26-P compared with the SS rat kidney. Immunohistochemistry studies localized PAPPA2 in the ureteric bud (UB) and distal part of S-shaped body. PAPPA2 was colocalized with IGFBP-5 in the UB and Na+/K+/2Cl− cotransporter–stained tubules, respectively. Future studies are needed to determine the role of Pappa2 in kidney development and mechanistic pathways involved in this process.

scholarly journals Post-translational modifications by SIRT3 de-2-hydroxyisobutyrylase activity regulate glycolysis and enable nephrogenesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luca Perico ◽  
Marina Morigi ◽  
Anna Pezzotta ◽  
Daniela Corna ◽  
Valerio Brizi ◽  
...  
Keyword(s):  
Kidney Development ◽  
Renal Diseases ◽  
Nephron Number ◽  
Self Renewal ◽  
Post Translational Modifications ◽  
Nephron Endowment ◽  
Nephron Progenitors ◽  
Lysine Residues ◽  
Epigenetic Processes

AbstractAbnormal kidney development leads to lower nephron number, predisposing to renal diseases in adulthood. In embryonic kidneys, nephron endowment is dictated by the availability of nephron progenitors, whose self-renewal and differentiation require a relatively repressed chromatin state. More recently, NAD+-dependent deacetylase sirtuins (SIRTs) have emerged as possible regulators that link epigenetic processes to the metabolism. Here, we discovered a novel role for the NAD+-dependent deacylase SIRT3 in kidney development. In the embryonic kidney, SIRT3 was highly expressed only as a short isoform, with nuclear and extra-nuclear localisation. The nuclear SIRT3 did not act as deacetylase but exerted de-2-hydroxyisobutyrylase activity on lysine residues of histone proteins. Extra-nuclear SIRT3 regulated lysine 2-hydroxyisobutyrylation (Khib) levels of phosphofructokinase (PFK) and Sirt3 deficiency increased PFK Khib levels, inducing a glycolysis boost. This altered Khib landscape in Sirt3−/− metanephroi was associated with decreased nephron progenitors, impaired nephrogenesis and a reduced number of nephrons. These data describe an unprecedented role of SIRT3 in controlling early renal development through the regulation of epigenetics and metabolic processes.

scholarly journals Current Epigenetic Insights in Kidney Development

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1281
Author(s):  
Katrina Chan ◽  
Xiaogang Li
Keyword(s):  
Single Cell ◽  
Kidney Development ◽  
Kidney Diseases ◽  
Cell Lineage ◽  
Epigenetic Mechanisms ◽  
Phenotypic Stability ◽  
Lineage Specification ◽  
Adult Kidney ◽  
Single Cell Rna Sequencing ◽  
Histone Modification Patterns

The kidney is among the best characterized developing tissues, with the genes and signaling pathways that regulate embryonic and adult kidney patterning and development having been extensively identified. It is now widely understood that DNA methylation and histone modification patterns are imprinted during embryonic development and must be maintained in adult cells for appropriate gene transcription and phenotypic stability. A compelling question then is how these epigenetic mechanisms play a role in kidney development. In this review, we describe the major genes and pathways that have been linked to epigenetic mechanisms in kidney development. We also discuss recent applications of single-cell RNA sequencing (scRNA-seq) techniques in the study of kidney development. Additionally, we summarize the techniques of single-cell epigenomics, which can potentially be used to characterize epigenomes at single-cell resolution in embryonic and adult kidneys. The combination of scRNA-seq and single-cell epigenomics will help facilitate the further understanding of early cell lineage specification at the level of epigenetic modifications in embryonic and adult kidney development, which may also be used to investigate epigenetic mechanisms in kidney diseases.

Abstract 452: The Degree of Nephron Deficit is a Determinant of the Cardiovascular and Renal Risks Associated With a Reduced Nephron Endowment

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Michelle M Kett ◽  
Leek Makuei ◽  
Xiaochu Cai ◽  
Russell D Brown
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Kidney Development ◽  
Urine Excretion ◽  
Albumin Excretion ◽  
Nephron Endowment ◽  
Increased Sensitivity ◽  
Nephron Deficit ◽  
Enalapril Treatment

A reduced nephron endowment is associated with an increased sensitivity to hypertensive stimuli. We examined whether nephron endowment, and the degree of nephron deficit, impacts on the blood pressure and renal response to chronic angiotensin II (AngII) infusion. To address this aim we used the GDNF heterozygous mouse that, despite the same genotype, produces two distinct levels of nephron deficit due to the role of GDNF in both the initiation of kidney development and induction of nephron formation. GDNF het mice are born with either 2 small kidneys and a 30% nephron deficit (Het2K), or a single small kidney (Het1K) and a 65% nephron deficit compared to wild-type littermates (WT). Sixteen week old male GDNF WT (n=9), Het2K (n=5) and Het1K (n=7) mice were implanted with radiotelemetry probes and baseline pressures recorded. Mice were administered enalapril (10mg/kg/day, drinking water) alone for 3 days, then concomitant with an AngII infusion (600ng/kg/min; s.c. osmotic minipump) for a further 21 days. 24hr albumin and urine excretion were assessed at baseline and at the end of the 21 days of blood pressure recording. Baseline MAP was not different between WT, Het2K and Het1K groups (98.3±1.3, 97.1±1.8, 100.9±1.9mmHg respectively). Enalapril treatment led to a similar fall in MAP of 23mmHg in the 3 groups before the commencement of AngII infusion. AngII led to an immediate rise in MAP in all groups. At the end of the 21day infusion period, MAP of WT and Het2K mice were similar (122±3.3, 120.5±6.1mmHg), but MAP of Het1K mice (139.7±3.6mmHg; P<0.01) was significantly elevated over WT mice. Albumin excretion was not different between the groups at baseline, and AngII infusion did not significantly increase albumin excretion in WT or Het2K mice. However albumin excretion in Het1K mice increased 15 fold (4.86±1.56 to 76.05±30.3ug/24hr; P<0.001). Urine excretion also significantly increased in the Het1K (1.59±1.5 to 3.7±0.59ml/24h; P<0.001) in response to Angiotensin II, though WT and Het2k mice were not affected. AngII infusion in Het1K, but not Het2k mice, led to significant exacerbation of hypertension and albuminuria. Our data suggests that the degree of nephron deficit is an important determinant of the risks associated with a reduced nephron endowment.

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