Impacts of low birthweight on kidney development and intergenerational growth of the offspring.

Low birthweight (LBW) increases the risk of adult-onset diseases, including kidney diseases, with intergenerational consequences; however, the underlying mechanisms and effective interventions are unclear. To examine the cross-generational effects of LBW, we established an LBW mouse model through reduced uterine perfusion pressure (RUPP) and investigated the therapeutic potential of tadalafil, a phosphodiesterase 5 inhibitor, on LBW-associated consequences. RUPP-pups (R1) had lower fetal and birth weights, delayed renal development, and fewer glomeruli than Sham-pups.

Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet.

Patients with chronic kidney disease (CKD) commonly exhibit hypercoagulability. Increased levels of uremic toxins cause thrombogenicity by increasing tissue factor (TF) expression and activating the extrinsic coagulation cascade. TF is induced in monocytes and macrophages under pathological conditions, such as inflammatory diseases.

Generation of Transgenic Mice that Conditionally Overexpress Tenascin-C.

Tenascin-C (TNC) is an extracellular matrix glycoprotein that is expressed during embryogenesis. It is not expressed in normal adults, but is up-regulated under pathological conditions. Although TNC knockout mice do not show a distinct phenotype, analyses of disease models using TNC knockout mice combined with experiments revealed the diverse functions of TNC.

Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease.

Nicotinamide adenine dinucleotide (NAD) supplies energy for deoxidation and anti-inflammatory reactions fostering the production of adenosine triphosphate (ATP). The kidney is an essential regulator of body fluids through the excretion of numerous metabolites. Chronic kidney disease (CKD) leads to the accumulation of uremic toxins, which induces chronic inflammation.

Lack of Endothelial Nitric Oxide Synthase Accelerates Ectopic Calcification in Uremic Mice Fed an Adenine and High Phosphorus Diet.

Ectopic calcification is a risk of cardiovascular disease in chronic kidney disease (CKD) patients, and impaired endothelial nitric oxide synthase (eNOS) is involved in the CKD complications. However, whether eNOS dysfunction is a cause of ectopic calcification in CKD remains to be elucidated. To address this issue, we investigated the role of eNOS in ectopic calcification in mice with renal injury caused by an adenine and high-phosphorus (Ade + HP) diet.

The effect of aldosterone on adiposity - The role of glucose absorption in the small intestine.

We have previously demonstrated that manipulation of the renin angiotensin system (RAS) has large effects on digestive efficiency. However, the effects of aldosterone on body weight, adiposity, and glucose absorption in the intestine remains unknown. We here demonstrated that lack of aldosterone synthase (ASKO) in mice did not affect adiposity.

Protease-activated receptor 2 contributes to placental development and fetal growth in mice.

Background: Protease-activated receptor 2 (PAR2) is activated by serine proteases such as coagulation tissue factor/VIIa complex, factor Xa or trypsin and is pro-angiogenic in several disease models. Impaired angiogenesis in placenta causes placental dysfunction and fetal growth restriction. PAR2 is expressed in the placenta trophoblast.

Metabolomics of a mouse model of preeclampsia induced by overexpressing soluble fms-like tyrosine kinase 1.

Preeclampsia (PE) is a leading cause of maternal morbidity and mortality. Nicotinamide has beneficial effects on PE. In this study, we evaluated the effect of nicotinamide on placental development using a PE mouse model.

Dual blockade of protease-activated receptor 1 and 2 additively ameliorates diabetic kidney disease.

Protease-activated receptors (PARs) are coagulation protease targets, and they increase expression of inflammatory cytokines and chemokines in various diseases. Of all PARs, previous reports have shown that PAR1 or PAR2 inhibition is protective against diabetic glomerular injury. However, how PAR1 and PAR2 cooperatively contribute to diabetic kidney disease (DKD) pathogenesis and whether dual blockade of PARs is more effective in DKD remain elusive.

Effects of the oral adsorbent AST-120 on fecal p-cresol and indole levels and on the gut microbiota composition.

In chronic kidney disease, elevated levels of circulating uremic toxins are associated with a variety of symptoms and organ dysfunction. Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are microbiota-derived metabolites and representative uremic toxins. We have previously shown that the oral adsorbent AST-120 profoundly reduced pCS compared to IS in adenine-induced renal failure in mice.

Protease-activated receptor 2 protects against VEGF inhibitor-induced glomerular endothelial and podocyte injury.

Vascular endothelial growth factor (VEGF) inhibitors cause glomerular injury. We have recently shown that activation of protease-activated receptor 2 (PAR2) by factor Xa exacerbated diabetic kidney disease. However, the role of PAR2 in glomerular injury induced by VEGF blockade is not known.

Nicotinamide alleviates kidney injury and pregnancy outcomes in lupus-prone MRL/lpr mice treated with lipopolysaccharide.

Systemic lupus erythematosus (SLE) increases the risk of preterm birth and preeclampsia (PE). The flares of SLE during pregnancy or after delivery are also problematic. We have previously demonstrated that nicotinamide (NAM), a non-teratogenic amide of vitamin B3, reduces inflammation and oxidative stress and improves PE-like phenotype and pregnancy outcomes in the mouse models of PE.

Protease-activated receptor 2 exacerbates cisplatin-induced nephrotoxicity.

Acute kidney injury (AKI) is associated with hypercoagulability. Tissue factor/factor VIIa complex and factor Xa in the coagulation cascade activate protease-activated receptor 2 (PAR2). Previously, we have shown that PAR2-mediated inflammation aggravates kidney injury in models of diabetic kidney disease and adenine-induced renal fibrosis.

Vitamin B Nicotinamide: A Promising Candidate for Treating Preeclampsia and Improving Fetal Growth.

Up to 8% of pregnant women suffer from preeclampsia (PE), a deadly disease characterized by high blood pressure (BP), blood vessel damage, called endotheliosis (vascular endothelial swelling with narrowing of capillary lumen), and high levels of protein in the urine. PE is often associated with premature delivery, which is a risk factor of cardiovascular and metabolic diseases among the offspring. Accordingly, establishing drug treatments of PE is in immediate needs.

Impact of the Oral Adsorbent AST-120 on Organ-Specific Accumulation of Uremic Toxins: LC-MS/MS and MS Imaging Techniques.

Elevated circulating uremic toxins are associated with a variety of symptoms and organ dysfunction observed in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and -cresyl sulfate (PCS) are representative uremic toxins that exert various harmful effects. We recently showed that IS induces metabolic alteration in skeletal muscle and causes sarcopenia in mice.

Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia.

Preeclampsia (PE) complicates ∼5% of human pregnancies and is one of the leading causes of pregnancy-related maternal deaths. The only definitive treatment, induced delivery, invariably results in prematurity, and in severe early-onset cases may lead to fetal death. Many currently available antihypertensive drugs are teratogenic and therefore precluded from use.

Offspring derived from intracytoplasmic injection of transgenic rat sperm.

The objective of the present study was to produce rat offspring by intracytoplasmic sperm injection (ICSI) using a Piezo-driven micromanipulator. Transgenic male rats carrying a green fluorescent protein gene (GFP: homozygous) were used as sperm donors. The epididymal spermatozoa were suspended and sonicated in m-KRB medium and were frozen in the same medium at -20 degrees C until use.