scholarly journals Intrauterine Low-Protein Diet Exacerbates Abnormal Development of the Urinary System in Gen1-Mutant Mice

2021 ◽  
pp. 1-12
Author(s):  
Minghui Yu ◽  
Yaxin Li ◽  
Lihong Tan ◽  
Jing Chen ◽  
Yihui Zhai ◽  
...  
Keyword(s):  
Kidney Development ◽  
Early Stage ◽  
Mutant Mice ◽  
Protein Diet ◽  
Abnormal Development ◽  
Wild Type ◽  
Serum Free ◽  
Isocaloric Diet ◽  
Dominant Phenotype ◽  
Low Protein

<b><i>Background:</i></b> <i>Gen1</i> mutation can cause various phenotypes of congenital anomaly of the kidney and urinary tract (CAKUT). An intrauterine low-protein isocaloric diet can also cause CAKUT phenotypes in offspring. However, single factors such as gene mutation or abnormal environmental factor during pregnancy can only explain part of the pathogenesis of CAKUT. <b><i>Objectives:</i></b> A low-protein isocaloric diet was fed to <i>Gen1</i>-mutant mice throughout pregnancy to establish a <i>Gen1</i>-mutant mouse model exposed to a low-protein isocaloric intrauterine environment. The mice were divided into 4 groups: normal (22%) protein diet (ND) + wild-type mice (CON group), ND + Gen1<sup>PB/+</sup> mice (Gen1<sup>PB/+</sup> group), low (6%)-protein isocaloric diet (LD) + wild-type mice (LD group), and the LD + Gen1<sup>PB/+</sup> groups. <b><i>Methods:</i></b> The experimental design included observing proportion and distribution of CAKUT phenotypes of neonatal mice; evaluating the number of ureteric buds (UBs) on embryonic day (E) 11.5, the location of UBs on E11.5, and length of the common nephric duct (CND); isolating embryonic kidneys on E11.5 from the Gen1<sup>PB/+</sup> group and culturing embryonic kidneys in medium containing 10% serum or serum-free medium to observe the branching of UBs; and detecting the p-PLCγ, p-Akt, and p-ERK1/2 in UBs and CND on E11.5, as well as the apoptosis and proliferation of tissues by immunofluorescence staining. <b><i>Results:</i></b> We found that the incidence of CAKUT in offspring of Gen1<sup>PB/+</sup> mice under an intrauterine low-protein isocaloric diet environment was significantly increased, and a duplicated collecting system was the dominant phenotype of CAKUT. During the early stage of metanephric development, ectopic protrusion of UBs may appear and lower locations of UBs in Gen1<sup>PB/+</sup> mice under an intrauterine low-protein isocaloric diet environment and the number of UB branches in the serum-free culture condition significantly decreased. Further examination revealed that p-PLCγ signaling and tissue apoptosis were abnormal in UBs and the CND at the early stage of kidney development. <b><i>Conclusions:</i></b> The aforementioned findings suggest that an intrauterine low-protein isocaloric diet can aggravate the occurrence of CAKUT in <i>Gen1</i>-mutant mice, which might affect key steps in the metanephric development, such as the protrusion of UBs, which might be related to mediate UBs and CND apoptosis through p-PLCγ signaling.

scholarly journals Intrauterine low-protein diet aggravates developmental abnormalities of the urinary system via the Akt/Creb3 pathway in Robo2 mutant mice

2020 ◽  
Vol 318 (1) ◽  
pp. F43-F52 ◽  
Author(s):  
Minghui Yu ◽  
Lihong Tan ◽  
Yaxin Li ◽  
Jing Chen ◽  
Yihui Zhai ◽  
...  
Keyword(s):  
Mutant Mouse ◽  
Mutant Mice ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Low Protein ◽  
Element Binding Protein ◽  
Duplicated Collecting System ◽  
Responsive Element ◽  
Camp Responsive Element Binding ◽  
Collecting System

The offspring of Robo2 mutant mice usually present with variable phenotypes of congenital anomalies of the kidney and urinary tract (CAKUT). An intrauterine low-protein diet can also cause CAKUT in offspring, dominated by the duplicated collecting system phenotype. A single genetic or environment factor can only partially explain the pathogenesis of CAKUT. The present study aimed to establish an intrauterine low-protein diet roundabout 2 ( Robo2) mutant mouse model and found that the intrauterine low-protein diet led to significantly increased CAKUT phenotypes in Robo2PB/+ mice offspring, dominant by a duplicated collecting system. At the same time, more ectopic and lower located ureteric buds (UBs) were observed in the intrauterine low-protein diet-fed Robo2 mutant mouse model, and the number of UB branches was reduced in the serum-free culture. During UB protrusion, intrauterine low-protein diet reduced the expression of Slit2/Robo2 in Robo2 mutant mice and affected the expression of glial cell-derived neurotrophic factor/Ret, which is a key molecule for metanephric development, with increasing phospho-Akt and phospho-cAMP responsive element-binding protein 3 activity and a reduction of apoptotic cells in embryonic day 11.5 UB tissues. The mechanism by which an intrauterine low-protein diet aggravates CAKUT in Robo2 mutant mice may be related to the disruption of Akt/cAMP responsive element-binding protein 3 signaling and a reduction in apoptosis in UB tissue.

scholarly journals Impaired Urea Accumulation in the Inner Medulla of Mice Lacking the Urea Transporter UT-A2

2005 ◽  
Vol 25 (16) ◽  
pp. 7357-7363 ◽  
Author(s):  
Shinichi Uchida ◽  
Eisei Sohara ◽  
Tatemitsu Rai ◽  
Masahito Ikawa ◽  
Masaru Okabe ◽  
...  
Keyword(s):  
Physiological Role ◽  
Urine Osmolality ◽  
Protein Diet ◽  
Wild Type ◽  
Urea Transporter ◽  
High Concentration ◽  
Reverse Transcription Pcr ◽  
Low Protein ◽  
Urea Recycling

ABSTRACT Urea transporter UT-A2, the major urea transporter of the thin descending limb of the loop of Henle in short loop nephrons, has been implicated in urea recycling in the medulla, thereby producing concentrated urine. To investigate the physiological role of UT-A2 in vivo, we generated UT-A2-selective knockout mice by deleting the UT-A2 promoter. Western analysis, immunohistochemistry, and quantitative reverse transcription-PCR were used to confirm the specific deletion of UT-A2 with preservation of other UT-A transporters. Compared to wild-type mice, differences in the urine outputs of UT-A2−/− mice consuming a normal protein diet (20% protein) were not observed under normal conditions or with dehydration. Likewise, impairment of urea accumulation in the inner medulla of UT-A2−/− mice was not observed. On a low-protein diet (4% protein), however, significantly reduced maximal urine osmolality was observed in dehydrated UT-A2−/− mice compared to wild-type littermates (2,500 mosmol versus 3,450 mosmol, respectively). A significant reduction in urea accumulation in the inner medulla was also observed in UT-A2−/− mice; however, differences in Na+ and Cl− accumulation were not observed. Thus, UT-A2 is important for maintaining a high concentration of urea in the inner medulla when urea supply to the kidney is limited.

scholarly journals PAX2 is reactivated in urinary tract obstruction and partially protects collecting duct cells from programmed cell death

2007 ◽  
Vol 292 (4) ◽  
pp. F1267-F1273 ◽  
Author(s):  
Tiffany Cohen ◽  
Oleg Loutochin ◽  
Moamen Amin ◽  
John-Paul Capolicchio ◽  
Paul Goodyer ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Kidney Development ◽  
Urinary Tract Obstruction ◽  
Collecting Duct ◽  
Mutant Mice ◽  
Sham Operation ◽  
Wild Type ◽  
Duct Cells ◽  
Collecting Duct Cells ◽  
Pax2 Expression

Obstruction of the urinary tract activates apoptotic pathways in collecting duct cells and leads to loss of renal parenchyma before surgical intervention. It has been suggested that developmental pathways may be reactivated to offset acute organ damage. One such molecule, PAX2, is expressed throughout the fetal collecting duct and was recently shown to suppress apoptosis during kidney development. We hypothesized that acute unilateral urinary tract obstruction (UUO) reactivates PAX2 expression in the mature kidney and partially suppresses apoptosis. If so, animals with PAX2 mutations should have increased susceptibility to parenchymal damage. Wild-type and heterozygous Pax2 mutant (C3H/ Pax2 1Neu) mice underwent unilateral ureteric ligation or sham operation at 6 wk of age; kidneys were examined after 5, 10, and 15 days. Whereas PAX2 protein levels fell to low levels in the first weeks of life, it was sharply reactivated by day 10 in collecting duct cells of wild-type but not in Pax2 1Neu mutant mice with UUO. Wild-type mice with UUO had marked TUNEL and cleaved spectrin staining in tubular cells and reduced kidney weight after 10–15 days. Mutant mice had exaggerated increases in markers of apoptosis and exaggerated loss of renal parenchymal loss in the obstructed kidney. These observations suggest that PAX2 is rapidly reactivated in UUO and that mice with genetically limited PAX2 expression have heightened susceptibility to apoptosis.

Hepatic Ultrastructure Changes Induced by Lithocholic Acid

1967 ◽  
Vol 25 ◽  
pp. 162-163 ◽  
Author(s):  
F. G. Zaki
Keyword(s):  
Endoplasmic Reticulum ◽  
Lithocholic Acid ◽  
Smooth Endoplasmic Reticulum ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Electron Microscopic ◽  
Hydropic Degeneration ◽  
Hepatic Cells ◽  
Low Protein ◽  
Microscopic Studies

Addition of lithocholic acid (LCA), a naturally occurring bile acid in mammals, to a low protein diet fed to rats induced marked inflammatory reaction in the hepatic cells followed by hydropic degeneration and ductular cell proliferation. These changes were accompanied by dilatation and hyperplasia of the common bile duct and formation of “gallstones”. All these changes were reversible when LCA was withdrawn from the low protein diet except for the hardened gallstones which persisted.Electron microscopic studies revealed marked alterations in the hepatic cells. Early changes included disorganization, fragmentation of the rough endoplasmic reticulum and detachment of its ribosomes. Free ribosomes, either singly or arranged in small clusters were frequently seen in most of the hepatic cells. Vesiculation of the smooth endoplasmic reticulum was often encountered as early as one week after the administration of LCA (Fig. 1).

Economic Effects of Treatment of Chronic Kidney Disease with Low-Protein Diet

2013 ◽  
Author(s):  
Francesco Saverio Mennini ◽  
Simone Russo ◽  
Andrea Marcellusi ◽  
Giuseppe Quintaliani ◽  
Denis Fouque
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Economic Effects ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Low Protein

scholarly journals PSIV-6 Effect of a Phytogenic Water Additive on Growth Performance, Blood Metabolites and Gene Expression of Amino Acids Transporters in Nursery Pigs Fed with Low Protein Diets

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 281-282
Author(s):  
Cedrick N Shili ◽  
Mohammad Habibi ◽  
Julia Sutton ◽  
Jessie Barnes ◽  
Jacob Burchkonda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Growth Performance ◽  
Mrna Abundance ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Blood Calcium ◽  
Low Protein ◽  
Protein Diets ◽  
Standard Protein

Abstract Moderately low protein (MLP) diets can help decrease nutrient excretion from the swine production. However, MLP diets negatively impact growth performance. We hypothesized that supplementing MLP diets with phytogenics may reduce the negative effects of these diets on growth. The objective of this study was to investigate the effect of a phytogenic water additive (PWA; Herbanimal®) on growth performance, blood metabolite and gene expression of amino acids transporters in pigs fed with MLP diets. Forty-eight weaned barrows were allotted to six dietary treatments (n = 8) for 4 weeks: &gt;CON-NS: standard protein diet-no PWA; CON-LS: standard protein diet-low PWA dose (4 ml/L); CON-HS: standard protein diet-high PWA dose (8 ml/L); LP-NS: low protein diet-no PWA; LP-LS: low protein diet-low PWA dose (4 ml/L); LP-HS: low protein diet- high PWA dose (8 ml/L). Feed intake and body weight were recorded daily and weekly, respectively. At week 4, blood and tissue samples were collected and analyzed for metabolites using a chemistry analyzer and amino acid transporters using qPCR, respectively. The data were analyzed by univariate GLM (SPSS®) and the means were separated using paired Student’s t-test corrected by Benjamini-Hochberg. Pigs fed CON-HS improved the average daily gain and serum calcium and phosphorus concentrations compared to CON-NS. Pigs fed LP-LS had higher serum phosphorus and blood urea nitrogen compared to the pigs fed with LP-NS. The mRNA abundance of SLC7A11 in the jejunum was lower in CON-LS and CON-HS compared to CON-NS. Additionally, mRNA abundance of SLC6A19 in the jejunum of pigs fed with LP-LS was higher compared to LP-NS and lower in CON-HS relative to pigs fed with CON-LS. In conclusion, PWA improved the growth performance of pigs fed standard protein diets but not low protein diets. Further, the PWA improved the concentrations of blood calcium and phosphorous in pigs fed MLP diets. Funding: Agrivida and Animal Health and Production and Animal Products: Improved Nutritional Performance, Growth, and Lactation of Animals from the USDA-NIFA.

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