scholarly journals Gestational Low Protein Diet Modulation on miRNA Transcriptome and Its Target During Fetal and Breastfeeding Nephrogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Letícia de Barros Sene ◽  
Gabriela Leme Lamana ◽  
Andre Schwambach Vieira ◽  
Wellerson Rodrigo Scarano ◽  
José Antônio Rocha Gontijo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Target Genes ◽  
Maternal Diet ◽  
Protein Restriction ◽  
Protein Diet ◽  
Compensatory Mechanisms ◽  
Adult Age ◽  
Renal Progenitor Cells ◽  
Low Protein

BackgroundThe kidney ontogenesis is the most structurally affected by gestational protein restriction, reducing 28% of their functional units. The reduced nephron number is predictive of hypertension and cardiovascular dysfunctions that are generally observed in the adult age of most fetal programming models. We demonstrate miRNAs and predict molecular pathway changes associated with reduced reciprocal interaction between metanephros cap (CM) and ureter bud (UB) and a 28% decreased nephron stem cells in the 17 gestational days (17GD) low protein (LP) intake male fetal kidney. Here, we evaluated the same miRNAs and predicted targets in the kidneys of 21GD and at 7 days of life (7DL) LP offspring to elucidate the molecular modulations during nephrogenesis.MethodsPregnant Wistar rats were allocated into two groups: NP (regular protein diet- 17%) or LP (diet-6%). miRNA transcriptome sequencing (miRNA-Seq) was performed on the MiSeq platform from 21GD and 7DL male offspring kidneys using previously described methods. Among the top 10 dysfunctional regulated miRNAs, we validated 7 related to proliferation, differentiation, and apoptosis processes and investigated predicted target genes and proteins by RT-qPCR and immunohistochemistry.ResultsIn 21GD, LP fetuses were identified alongside 21 differently expressed miRNAs, of which 12 were upregulated and 9 downregulated compared to age-matched NP offspring. In 7-DL LP offspring, the differentially expressed miRNAs were counted to be 74, of which 46 were upregulated and 28 downregulated. The curve from 17-GD to 7-DL shows that mTOR was fundamental in reducing the number of nephrons in fetal kidneys where the mothers were subjected to a protein restriction. IGF1 and TGFβ curves also seemed to present the same mTOR pattern and were modulated by miRNAs 181a-5p, 181a-3p, and 199a-5p. The miRNA 181c-3p modulated SIX2 and Notch1 reduction in 7-DL but not in terms of the enhanced expression of both in the 21-GD, suggesting the participation of an additional regulator. We found enhanced Bax in 21-GD; it was regulated by miRNA 298-5p, and Bcl2 and Caspase-3 were controlled by miRNA (by 7a-5p and not by the predicted 181a-5p). The miRNA 144-3p regulated BCL6, which was enhanced, as well as Zeb 1 and 2 induced by BCL6. These results revealed that in 21GD, the compensatory mechanisms in LP kidneys led to the activation of UB ramification. Besides, an increase of 32% in the CM stem cells and a possible cell cycle halt of renal progenitor cells, which remaining undifferentiated, were observed. In the 7DL, much more altered miRNA expression was found in LP kidneys, and this was probably due to an increased maternal diet content. Additionally, we verified the activation of pathways related to differentiation and consumption of progenitor cells.

scholarly journals Impact of gestational low-protein intake on embryonic kidney microRNA expression and in the nephron progenitor cells of the male offspring fetus

2020 ◽  
Author(s):  
Leticia B Sene ◽  
Wellerson R Scarano ◽  
Adriana Zapparoli ◽  
Jose AR Gontijo ◽  
Patricia A Boer
Keyword(s):  
Target Genes ◽  
Expression Patterns ◽  
Cell Number ◽  
Protein Restriction ◽  
Protein Diet ◽  
Ki 67 ◽  
Low Protein ◽  
Maternal Protein Restriction ◽  
Cell Proliferation And Differentiation ◽  
Protein Supply

Abstract Background: Authors demonstrated that gestational low-protein (LP) intake offspring presents a lower birthweight, reduced nephrons numbers and renal salt excretion, arterial hypertension and renal failure development when compared to normal protein (NP) intake rats in adulthood. The current study evaluated the miRNAs and predicted gene expression patterns in the 17-days LP (17-DG) fetal kidney to elucidate the molecular pathways and renal cell proliferation and differentiation profile. Methods: Pregnant Wistar rats were allocated into two groups, according to protein supply during pregnancy: NP (normal protein diet- 17%) or LP (low protein diet-6%). miRNA transcriptome sequencing (miRNA-Seq) was performed on the MiSeq platform and, RT-qPCR of predicted target genes, immunohistochemistry and morphological quantification from 17-DG offspring kidneys using previously described methods. Results: Forty-four expressed miRNAs, which 19 miRNA were up- and 25 downregulated, were identified in 17-DG LP fetuses compared to age-matched NP offspring. The study selected 7 miRNAs related to proliferation, differentiation, and cellular apoptosis processes. The study showed a reduced cell number, Six-2 and c-Myc immunoreactivity in metanephros cap (CM) and ureter bud (UB) in 17-DG LP fetuses. Also, Ki-67 immunoreactivity in CM was 48% lesser in LP compared to NP age-matched fetus. Conversely, in LP CM and UB β-catenin was 154% and 85% markedly enhanced, respectively and, mTOR immunoreactivity was also higher in LP CM (139%) and UB (104%) compared to the NP offspring. UB TGFβ-1 staining cells increased (about 30%) in the LP offspring. Otherwise, Zeb1 metanephros-stained, enhanced 30% in LP offspring without Zeb2 staining in both groups. Conclusions: The present study demonstrates that maternal protein restriction change miRNAs, mRNAs, and critical proteins expression involved in the processes of proliferation, differentiation, and apoptosis that occurs during renal development. The renal ontogenic dysfunction caused by maternal protein restriction promotes a reduced reciprocal interaction between CM and UB, and consequently, a programmed and expressive decrease in the nephron number fetuses.

scholarly journals Survival on dialysis among chronic renal failure patients treated with a supplemented low-protein diet before dialysis.

1995 ◽  
Vol 6 (5) ◽  
pp. 1379-1385
Author(s):  
J Coresh ◽  
M Walser ◽  
S Hill
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Mortality Rate ◽  
Serum Creatinine ◽  
Dietary Treatment ◽  
Mortality Rates ◽  
Protein Restriction ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Low Protein

Concerns have been raised about the possibility of protein restriction resulting in malnutrition and poor subsequent survival on dialysis. However, no studies have examined patients treated with protein restriction to determine their subsequent survival on dialysis. This study prospectively monitored 67 patients with established chronic renal failure (mean initial serum creatinine of 4.3 mg/dL) who were treated with a very low-protein diet (0.3 g/kg per day) supplemented with either essential amino acids or a ketoacid-amino acid mixture and observed closely for clinical complications. Forty-four patients required dialysis. Once dialysis was started, dietary treatment was no longer prescribed. The cumulative mortality rate during the first 2 yr after starting dialysis was 7% (95% confidence interval, 0 to 16%). During this period, only two deaths occurred compared with 11.5 deaths expected on the basis of national mortality rates adjusted for age, sex, race, and cause of renal disease (P = 0.002). However, the protective effect was limited to the first 2 yr on dialysis. Thereafter, mortality rates increased, resulting in a total of 10 deaths during 96.4 person-years of follow-up, which was not significantly lower than the 14.9 deaths expected (P = 0.25). Extrapolation of sequential serum creatinine measurements made before dietary treatment suggests that the improved survival cannot be due to the early initiation of dialysis. Although the lack of an internal control group and data on dialysis lends uncertainty, the large difference in mortality rate between these patients and the nationwide experience indicates that protein restriction and close clinical monitoring predialysis does not worsen and may substantially improve survival during the first 2 yr on dialysis. These findings point out the importance of studying predialysis treatments as a means for lowering mortality on dialysis.

Green tea extract intake during lactation modified cardiac macrophage infiltration and AMP-activated protein kinase phosphorylation in weanling rats from undernourished mother during gestation and lactation

2016 ◽  
Vol 8 (2) ◽  
pp. 178-187 ◽  
Author(s):  
E. Matsumoto ◽  
S. Kataoka ◽  
Y. Mukai ◽  
M. Sato ◽  
S. Sato
Keyword(s):  
Protein Kinase ◽  
Green Tea ◽  
Control Diet ◽  
Protein Restriction ◽  
Protein Diet ◽  
Macrophage Infiltration ◽  
Low Protein Diet ◽  
Low Protein ◽  
Tea Extract ◽  
Amp Activated Protein Kinase

Maternal dietary restriction is often associated with cardiovascular disease in offspring. The aim of this study was to investigate the effect of green tea extract (GTE) intake during lactation on macrophage infiltration, and activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and serine-threonine kinase Akt (Akt) in the hearts of weanlings exposed to maternal dietary protein restriction. Pregnant Wistar rats were fed control (C) or low-protein diets (LP) throughout gestation. Following delivery, the dams received a control or a GTE-containing control diet during lactation: control diet during gestation and lactation (CC), low-protein diet during gestation and lactation (LPC), low-protein diet during gestation and 0.12% GTE-containing low-protein diet during lactation (LPL), and low-protein diet during gestation and 0.24% GTE-containing low-protein diet during lactation (LPH). The female offspring were sacrificed at day 22. Biochemical parameters in the plasma, macrophage infiltration, degree of fibrosis and expression levels of AMPK and Akt were examined. The plasma insulin level increased in LPH compared with LPC. Percentage of the fibrotic areas and the number of macrophages in LPC were higher than those in CC. Conversely, the fibrotic areas and the macrophage number in LPH were smaller (21 and 56%, respectively) than those in LPC. The levels of phosphorylated AMPK in LPL and LPH, and Akt in LPH were greater than those in LPC. In conclusion, maternal protein restriction may induce macrophage infiltration and the decrease of insulin levels. However, GTE intake during lactation may suppress macrophage infiltration and restore insulin secretion function via upregulation of AMPK and insulin signaling in weanlings.

scholarly journals Role of bone marrow-derived stem cells, renal progenitor cells and stem cell factor in chronic renal allograft nephropathy

2013 ◽  
Vol 49 (3) ◽  
pp. 235-247
Author(s):  
Hayam Abdel Meguid El Aggan ◽  
Mona Abdel Kader Salem ◽  
Nahla Mohamed Gamal Farahat ◽  
Ahmad Fathy El-Koraie ◽  
Ghaly Abd Al-Rahim Mohammed Kotb
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Stem Cell Factor ◽  
Renal Allograft ◽  
Renal Progenitor Cells ◽  
Renal Progenitor

scholarly journals A low-protein diet supplemented with ketoacids plays a more protective role against oxidative stress of rat kidney tissue with 5/6 nephrectomy than a low-protein diet alone

2009 ◽  
Vol 103 (4) ◽  
pp. 608-616 ◽  
Author(s):  
Xiang Gao ◽  
Jianxiang Wu ◽  
Zheyi Dong ◽  
Can Hua ◽  
Huimin Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Tissue ◽  
Protein Restriction ◽  
Protein Malnutrition ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Glomerular Sclerosis ◽  
Control Group ◽  
Stress Injury ◽  
Low Protein

Dietary protein restriction is one major therapy in chronic kidney disease (CKD), and ketoacids have been evaluated in CKD patients during restricted-protein diets. The objective of the present study was to compare the efficacy of a low-protein diet supplemented with ketoacids (LPD+KA) and a low-protein diet alone (LPD) in halting the development of renal lesions in CKD. 5/6 Nephrectomy Sprague–Dawley rats were randomly divided into three groups, and fed with either 22 % protein (normal-protein diet; NPD), 6 % protein (LPD) or 5 % protein plus 1 % ketoacids (LPD+KA) for 24 weeks. Sham-operated rats were used as controls. Each 5/6 nephrectomy group included fifteen rats and the control group included twelve rats. Proteinuria, decreased renal function, glomerular sclerosis and tubulointerstitial fibrosis were found in the remnant kidneys of the NPD group. Protein restriction ameliorated these changes, and the effect was more obvious in the LPD+KA group after 5/6 nephrectomy. Lower body weight and serum albumin levels were found in the LPD group, indicating protein malnutrition. Lipid and protein oxidative products were significantly increased in the LPD group compared with the LPD+KA group. These findings indicate that a LPD supplemented with ketoacids is more effective than a LPD alone in protecting the function of remnant kidneys from progressive injury, which may be mediated by ketoacids ameliorating protein malnutrition and oxidative stress injury in remnant kidney tissue.

Hitting a triple in the non-alcoholic fatty liver disease field: sucrose intake in adulthood increases fat content in the female but not in the male rat offspring of dams fed a gestational low-protein diet

2017 ◽  
Vol 9 (2) ◽  
pp. 151-159 ◽  
Author(s):  
L. Nicolás-Toledo ◽  
M. Cervantes-Rodríguez ◽  
E. Cuevas-Romero ◽  
D. L. Corona-Quintanilla ◽  
E. Pérez-Sánchez ◽  
...  
Keyword(s):  
Maternal Diet ◽  
Fat Content ◽  
Protein Diet ◽  
Liver Fat ◽  
Low Protein Diet ◽  
Male Rat ◽  
Liver Fat Content ◽  
Alcoholic Fatty Liver ◽  
Low Protein ◽  
Alcoholic Fatty Liver Disease

The excessive consumption of carbohydrates is related to non-alcoholic fatty liver disease (NAFLD) in infants and adults. The effect of combining maternal malnutrition and a high carbohydrate intake on the development of NAFLD in adulthood remains unknown. We therefore hypothesized that consumption of 5% sucrose by the offspring of dams fed a low-protein diet during pregnancy promotes liver fat accumulation and oxidative damage differently in females and males. To test this, 12-month-old female and male offspring of mothers fed a Control (C) or low-protein diet (Restricted, R) were provided with either tap water or 5% sucrose for a period of 10 weeks. Livers were excised to measure the fat content and 3-nitrotyrosine (3-NTyr) immunostaining; serum samples were also obtained to measure the concentration of malondialdehyde (MDA). Data were analyzed using a non-repeated measures three-way analysis of variance to determine significant differences (P<0.05) regarding to the interaction among maternal diet, sucrose consumption and sex. Results showed that the liver fat content of females from R mothers was higher than that of their male counterpart. Hepatic 3-NTyr immunostaining and serum MDA concentrations were not affected by the interaction involving maternal diet, sucrose consumption and sex. Otherwise, liver fat content was correlated with the hepatic 3-NTyr immunostaining and serum MDA concentrations only in females. Thus, sucrose intake in adulthood increases fat content in the female but not in the male rat offspring of dams fed with a low-protein diet during pregnancy. This research emphasizes the importance of a balanced diet during pregnancy and the influence of the diet on the adult offspring.

scholarly journals Renal Progenitor Cells Have Higher Genetic Stability and Lower Oxidative Stress than Mesenchymal Stem Cells during In Vitro Expansion

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Elís Rosélia Dutra de Freitas Siqueira Silva ◽  
Napoleão Martins Argôlo Neto ◽  
Dayseanny de Oliveira Bezerra ◽  
Sandra Maria Mendes de Moura Dantas ◽  
Lucilene dos Santos Silva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Dna Damage ◽  
Mesenchymal Stem Cells ◽  
Progenitor Cells ◽  
Genetic Stability ◽  
Renal Progenitor Cells ◽  
In Vitro Expansion ◽  
Renal Progenitor

In vitro senescence of multipotent cells has been commonly associated with DNA damage induced by oxidative stress. These changes may vary according to the sources of production and the studied lineages, which raises questions about the effect of growing time on genetic stability. This study is aimed at evaluating the evolution of genetic stability, viability, and oxidative stress of bone marrow mesenchymal stem cells (MSCBMsu) and renal progenitor cells of the renal cortex (RPCsu) of swine (Sus scrofa domesticus) in culture passages. P2, P5, and P9 were used for MSCBMsu and P1, P2, and P3 for RPCsu obtained by thawing. The experimental groups were submitted to MTT, apoptosis and necrosis assays, comet test, and reactive substance measurements of thiobarbituric acid (TBARS), nitrite, reduced glutathione (GSH), and catalase. The MTT test curve showed a mean viability of 1.14±0.62 and 1.12±0.54, respectively, for MSCBMsu and RPCsu. The percentages of MSCBMsu and RPCsu were presented, respectively, for apoptosis, an irregular and descending behavior, and necrosis, ascending and irregular. The DNA damage index showed higher intensity among the MSCBMsu in the P5 and P9 passages (p<0.05). In the TBARS evaluation, there was variation among the lines of RPCsu and MSCBMsu, presenting the last most significant variations (p<0.05). In the nitrite values, we identified only among the lines, in the passages P1 and P2, with the highest averages displayed by the MSCBMsu lineage (p<0.05). The measurement of antioxidant system activity showed high standards, identifying differences only for GSH values, in the RPCsu lineage, in P3 (p<0.05). This study suggests that the maintenance of cell culture in the long term induces lower regulation of oxidative stress, and RPCsu presents higher genetic stability and lower oxidative stress than MSCBMsu during in vitro expansion.

scholarly journals Maternal Protein Restriction Modulates Angiogenesis and AQP9 Expression Leading to a Delay in Postnatal Epididymal Development in Rat

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1094 ◽  
Author(s):  
Talita de Mello Santos ◽  
Marilia Martins Cavariani ◽  
Dhrielly Natália Pereira ◽  
Bruno César Schimming ◽  
Luiz Gustavo de Almeida Chuffa ◽  
...  
Keyword(s):  
Well Being ◽  
Protein Restriction ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Pregnant Rats ◽  
Low Protein ◽  
Maternal Protein Restriction ◽  
Aqp1 Expression ◽  
In The Beginning ◽  
Endothelial Growth Factor

The maternal nutritional status is essential to the health and well-being of the fetus. Maternal protein restriction during the perinatal stage causes sperm alterations in the offspring that are associated with epididymal dysfunctions. Vascular endothelial growth factor (VEGF) and its receptor, VEGFr-2, as well as aquaporins (AQPs) are important regulators of angiogenesis and the epididymal microenvironment and are associated with male fertility. We investigated the effects of maternal protein restriction on epididymal angiogenesis and AQP expression in the early stages of postnatal epididymal development. Pregnant rats were divided into two experimental groups that received either a normoprotein (17% protein) or low-protein diet (6% protein) during gestation and lactation. At postnatal day (PND)7 and PND14, male offspring were euthanized, the epididymides were subjected to morphometric and microvascular density analyses and to VEGF-A, VEGF-r2, AQP1 and AQP9 expression analyses. The maternal low-protein diet decreased AQP9 and VEGFr-2 expression, decreased epididymal microvascularity and altered the morphometric features of the epididymal epithelium; no changes in AQP1 expression were observed at the beginning of postnatal epididymal development. Maternal protein restriction alters microvascularization and affects molecules involved in the epidydimal microenvironment, resulting in morphometric alterations related to a delay in the beginning of epididymis postnatal development.

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