scholarly journals Sphingolipids and kidney disease: Possible role of preeclampsia and intrauterine growth restriction (IUGR)

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0006322020
Author(s):  
Rodrigo Yokota ◽  
Benjamin Bhunu ◽  
Hiroe Toba ◽  
Suttira Intapad
Keyword(s):  
Kidney Disease ◽  
Intrauterine Growth Restriction ◽  
De Novo ◽  
Kidney Diseases ◽  
Cellular Membrane ◽  
Growth Restriction ◽  
Sphingolipid Metabolism ◽  
Gene Encoding ◽  
Intrauterine Growth

Sphingolipids are now considered not only as constitutional components of the cellular membrane but also as essential bioactive factors regulating development and physiological functions. Ceramide is a vital intermediate of sphingolipid metabolism, synthesized by de novo and salvage pathways, producing multiple types of sphingolipids and their metabolites. Although mutations in gene encoding enzymes regulating sphingolipid synthesis and metabolism cause distinct diseases, an abnormal sphingolipid metabolism contributes to various pathological conditions, including kidney disease. Excessive accumulation of glycosphingolipids and promotion of the ceramide salvage and sphingosine-1-phosphate (S1P) pathways are found in the damaged kidney. Acceleration of the sphingosine kinase/S1P/S1P receptor (SphK/S1P/S1PR) axis plays a central role in deteriorating kidney functions. The SphK/S1P/S1PR signaling impairment is also found during pregnancy complications such as preeclampsia and intrauterine growth restriction (IUGR). This mini-review discusses the current state of knowledge regarding the role of sphingolipid metabolism on kidney diseases and the possible involvement of preeclampsia and IUGR conditions.

Epigenetic mechanisms involved in intrauterine growth restriction and aberrant kidney development and function

2020 ◽  
pp. 1-11
Author(s):  
Thu N. A. Doan ◽  
Jessica F. Briffa ◽  
Aaron L. Phillips ◽  
Shalem Y. Leemaqz ◽  
Rachel A. Burton ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Intrauterine Growth Restriction ◽  
Kidney Development ◽  
Dna Methyltransferases ◽  
Growth Restriction ◽  
Epigenetic Mechanisms ◽  
Specific Expression ◽  
Maternal Line ◽  
Intrauterine Growth ◽  
Increased Risk

Abstract Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency results in a placenta that is unable to provide adequate nutrients and oxygen to the fetus. These growth-restricted babies have an increased risk of hypertension and chronic kidney disease later in life. In rats, both male and female growth-restricted offspring have nephron deficits but only males develop kidney dysfunction and high blood pressure. In addition, there is transgenerational transmission of nephron deficits and hypertension risk. Therefore, epigenetic mechanisms may explain the sex-specific programming and multigenerational transmission of IUGR-related phenotypes. Expression of DNA methyltransferases (Dnmt1and Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, and Cdkn1c) were investigated in kidney tissues of sham and IUGR rats in F1 (embryonic day 20 (E20) and postnatal day 1 (PN1)) and F2 (6 and 12 months of age, paternal and maternal lines) generations (n = 6–13/group). In comparison to sham offspring, F1 IUGR rats had a 19% decrease in Dnmt3a expression at E20 (P < 0.05), with decreased Cdkn1c (19%, P < 0.05) and increased Kcnq1 (1.6-fold, P < 0.01) at PN1. There was a sex-specific difference in Cdkn1c and Snrpn expression at E20, with 29% and 34% higher expression in IUGR males compared to females, respectively (P < 0.05). Peg3 sex-specific expression was lost in the F2 IUGR offspring, only in the maternal line. These findings suggest that epigenetic mechanisms may be altered in renal embryonic and/or fetal development in growth-restricted offspring, which could alter kidney function, predisposing these offspring to kidney disease later in life.

The Role of the Anti-Angiogenic Factor Endostatin in Intrauterine Growth Restriction

2005 ◽  
Vol 12 (3) ◽  
pp. 195-197 ◽  
Author(s):  
Ariadne Malamitsi-Puchner ◽  
Theodora Boutsikou ◽  
Emmanuel Economou ◽  
Evangelos Makrakis ◽  
Zoe Iliodromiti ◽  
...  
Keyword(s):  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Angiogenic Factor ◽  
Intrauterine Growth

The brain development of infants with intrauterine growth restriction: role of glucocorticoids

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Ying-xue Ding ◽  
Hong Cui
Keyword(s):  
Endothelial Cells ◽  
Brain Injury ◽  
Intrauterine Growth Restriction ◽  
Growth And Development ◽  
Growth Restriction ◽  
Microvascular Endothelial Cells ◽  
Intrauterine Growth ◽  
Growth Restrictions ◽  
The Brain

Abstract Brain injury is a serious complication of intrauterine growth restriction (IUGR), but the exact mechanism remains unclear. While glucocorticoids (GCs) play an important role in intrauterine growth and development, GCs also have a damaging effect on microvascular endothelial cells. Moreover, intrauterine adverse environments lead to fetal growth restriction and the hypothalamus-pituitary-adrenal (HPA) axis resetting. In addition, chronic stress can cause a decrease in the number and volume of astrocytes in the hippocampus and glial cells play an important role in neuronal differentiation. Therefore, it is speculated that the effect of GCs on cerebral neurovascular units under chronic intrauterine stimulation is an important mechanism leading to brain injury in infants with growth restrictions.

scholarly journals A novel PIK3R1 mutation of SHORT syndrome in a Chinese female with diffuse thyroid disease: a case report and review of literature

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Liying Sun ◽  
Qianwen Zhang ◽  
Qun Li ◽  
Yijun Tang ◽  
Yirou Wang ◽  
...  
Keyword(s):  
Case Report ◽  
Short Stature ◽  
Thyroid Disease ◽  
Nonsense Mutation ◽  
Intrauterine Growth Restriction ◽  
De Novo ◽  
Protein Translation ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Short Syndrome

Abstract Background SHORT syndrome is a rare genetic disease named with the acronyms of short stature, hyper-extensibility of joints, ocular depression, Rieger anomaly and teething delay. It is inherited in an autosomal dominant manner confirmed by the identification of heterozygous mutations in PIK3R1. This study hereby presents a 15-year-old female with intrauterine growth restriction, short stature, teething delay, characteristic facial gestalts who was identified a novel de novo nonsense mutation in PIK3R1. Case presentation The proband was admitted to our department due to irregular menstrual cycle and hirsutism with short stature, who had a history of intrauterine growth restriction and presented with short stature, teething delay, characteristic facial gestalts, hirsutism, and thyroid disease. Whole-exome sequencing and Sanger sequencing revealed c.1960C > T, a novel de novo nonsense mutation, leading to the termination of protein translation (p. Gln654*). Conclusions This is the first case report of SHORT syndrome complicated with thyroid disease in China, identifying a novel de novo heterozygous nonsense mutation in PIK3R1 gene (p. Gln654*). The phenotypes are mildly different from other cases previously described in the literature, in which our patient presents with lipoatrophy, facial feature, and first reported thyroid disease. Thyroid disease may be a new clinical symptom of patients with SHORT syndrome.

Angiopoietin-2 in the perinatal period and the role of intrauterine growth restriction

2006 ◽  
Vol 85 (1) ◽  
pp. 45-48 ◽  
Author(s):  
Ariadne Malamitsi-Puchner ◽  
Theodora Boutsikou ◽  
Emmanuel Economou ◽  
Anastasia Tzonou ◽  
Evangelos Makrakis ◽  
...  
Keyword(s):  
Intrauterine Growth Restriction ◽  
Perinatal Period ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Angiopoietin 2

scholarly journals The detrimental role of angiotensin receptor agonistic autoantibodies in intrauterine growth restriction seen in preeclampsia

2009 ◽  
Vol 206 (12) ◽  
pp. 2809-2822 ◽  
Author(s):  
Roxanna A. Irani ◽  
Yujin Zhang ◽  
Sean C. Blackwell ◽  
Cissy Chenyi Zhou ◽  
Susan M. Ramin ◽  
...  
Keyword(s):  
Intrauterine Growth Restriction ◽  
Causative Factor ◽  
Growth Restriction ◽  
Hypertensive Disorder ◽  
Human Trophoblast ◽  
Fetal Circulation ◽  
Intrauterine Growth ◽  
Underlying Mechanisms ◽  
Agonistic Autoantibodies

Growth-restricted fetuses are at risk for a variety of lifelong medical conditions. Preeclampsia, a life-threatening hypertensive disorder of pregnancy, is associated with fetuses who suffer from intrauterine growth restriction (IUGR). Recently, emerging evidence indicates that preeclamptic women harbor AT1 receptor agonistic autoantibodies (AT1-AAs) that contribute to the disease features. However, the exact role of AT1-AAs in IUGR and the underlying mechanisms have not been identified. We report that these autoantibodies are present in the cord blood of women with preeclampsia and retain the ability to activate AT1 receptors. Using an autoantibody-induced animal model of preeclampsia, we show that AT1-AAs cross the mouse placenta, enter fetal circulation, and lead to small fetuses with organ growth retardation. AT1-AAs also induce apoptosis in the placentas of pregnant mice, human villous explants, and human trophoblast cells. Finally, autoantibody-induced IUGR and placental apoptosis are diminished by either losartan or an autoantibody-neutralizing peptide. Thus, these studies identify AT1-AA as a novel causative factor of preeclampsia-associated IUGR and offer two possible underlying mechanisms: a direct detrimental effect on fetal development by crossing the placenta and entering fetal circulation, and indirectly through AT1-AA–induced placental damage. Our findings highlight AT1-AAs as important therapeutic targets.

The role of methylentetrahydrofolate reductase (MTHFR) gene polymorphism in intrauterine growth restriction development

2018 ◽  
Vol 12_2018 ◽  
pp. 23-28
Author(s):  
Tyutyunnik V.L. Tyutyunnik ◽  
Kan N.E. Kan ◽  
Mantrova D.A. Mantrova ◽  
Lomova N.A. Lomova N ◽  
Klimantsev I.V. Klimantsev ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Intrauterine Growth Restriction ◽  
Mthfr Gene ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Mthfr Gene Polymorphism ◽  
Methylentetrahydrofolate Reductase
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