Differentiating the Influences of Aging and Adiposity on Brain Weights, Levels of Serum and Brain Cytokines, Gastrointestinal Hormones, and Amyloid Precursor Protein.

Aging and obesity exert important effects on disease. Differentiating these effects is difficult, however, because weight gain often accompanies aging. Here, we used a nested design of aged, calorically restricted, and refed rats to measure changes in brain and blood levels of cytokines and gastrointestinal hormones, brain amyloid precursor protein levels, and brain and body weights.

RNA-binding protein IGF2BP2/IMP2 is required for laminin-β2 mRNA translation and is modulated by glucose concentration.

Laminin-β2 (LAMB2) is a critical component of the glomerular basement membrane as content of LAMB2 in part determines glomerular barrier permeability. Previously, we reported that high concentrations of glucose reduce expression of this laminin subunit at the translational level. The present studies were undertaken to further define systems that control Lamb2 translation and the effect of high glucose on those systems.

De novo expression of podocyte proteins in parietal epithelial cells in experimental aging nephropathy.

A progressive decrease in podocyte number underlies the development of glomerulosclerosis and reduced kidney function in aging nephropathy. Recent data suggest that under certain disease states, parietal epithelial cells (PECs) begin to express proteins considered specific to podocytes. To determine whether this phenomenon increases in aging kidneys, 4-, 12-, and 20-mo ad libitum-fed and 20-mo calorie-restricted (CR) rats were studied.

Regional differences in dialysis care and mortality among American Indians and Alaska Natives.

American Indians/Alaska Natives (AIANs) compose a heterogeneous population that includes geographically distinct tribal communities, many with high rates of ESRD. Regional features of dialysis care and mortality are unknown in this population. Here, we describe the structure of dialysis care and mortality of adult AIANs who initiated maintenance dialysis during 1995-2008 in different regions of the US.

Alterations in chromatin are associated with increases in collagen III expression in aging nephropathy.

Aging nephropathy is a slowly progressive fibrotic process that affects all compartments of the kidney and eventually impairs kidney function; however, little is known about the mechanisms that contribute to this process. These studies examined the epigenetic control of expression of collagen III (Col3a1), a matrix protein that contributes to kidney fibrosis. Using real-time PCR, Western blotting, and chromatin immunoprecipitation assay of kidneys harvested from 4- and 24-mo-old ad libitum-fed F344 rats, we found increased transcription of Col3a1 that was associated with increased RNA polymerase II recruitment despite elevated posttranslational histone modification (H3K27me3) normally associated with gene silencing.

Insulin-like growth factor-binding protein-5-induced laminin gamma1 transcription requires filamin A.

Insulin-like growth factor-binding protein-5 (IGFBP-5) has IGF-1-independent intranuclear effects that are poorly defined. Treatment of cells with IGFBP-5 induces migration, prevents apoptosis, and leads to increased laminin subunit transcription. Similarly, filamin A (FLNa), an actin-binding protein that participates in cell attachment, plays important additional roles in signal transduction and modulation of transcriptional responses.

Laminin alpha4-null mutant mice develop chronic kidney disease with persistent overexpression of platelet-derived growth factor.

Each extracellular matrix compartment in the kidney has a unique composition, with regional specificity in the expression of various laminin isoforms. Although null mutations in the majority of laminin chains lead to specific developmental abnormalities in the kidney, Lama4-/- mice have progressive glomerular and tubulointerstitial fibrosis. These mice have a significant increase in expression of platelet-derived growth factor (PDGF)-BB, PDGF-DD, and PDGF receptor beta in association with immature glomerular and peritubular capillaries.

Mechanisms and control of protein translation in the kidney.

Translational control of protein synthesis is critical for cell division, homeostasis and survival. Recent data indicate that dysregulation of protein synthesis that leads to either increased or decreased expression of specific proteins contributes to the manifestations of various kidney diseases. Most of the control of protein synthesis occurs in the first or initiation phase, which is also the most complicated.

Reductions in laminin beta2 mRNA translation are responsible for impaired IGFBP-5-mediated mesangial cell migration in the presence of high glucose.

Insulin-like growth factor binding protein-5 (IGFBP-5) mediates mesangial cell migration through activation of cdc42, and laminin421 binding to alpha(6)beta(1)-integrin (Berfield AK, Hansen KM, Abrass CK. Am J Physiol Cell Physiol 291: C589-C599, 2006). Because glomerular expression of laminin beta(2) is reduced in diabetic rats (Abrass CK, Spicer D, Berfield AK, St.

Lipid metabolism and renal disease.

Metabolic syndrome is associated with dyslipidemia, which is thought to contribute in part to the development of chronic kidney disease (CKD). This review discusses the factors that regulate intracellular handling of lipids and their relationship to disordered mesangial cell function. Specific attention is paid to those factors such as fatty acid translocase/scavenger receptor BII, proliferator-activated receptor delta, insulin-like growth factor-1, inflammation and hypertriglyceridemia that are altered in the metabolic syndrome.

Abnormal development of glomerular endothelial and mesangial cells in mice with targeted disruption of the lama3 gene.

Mice with targeted disruption of the lama3 gene, which encodes the alpha3 chain of laminin-5 (alpha3beta3gamma2, 332), develop a blistering skin disease similar to junctional epidermolysis bullosa in humans. These animals also develop abnormalities in glomerulogenesis. In both wild-type and mutant animals (lama3(-/-)), podocytes secrete glomerular basement membrane and develop foot processes.

Rat glomerular mesangial cells require laminin-9 to migrate in response to insulin-like growth factor binding protein-5.

Temporal and spatial differences in extracellular matrix play critical roles in cell proliferation, differentiation and migration. Different migratory stimuli use different substrates and receptors to achieve cell migration. To understand the mechanism of insulin-like growth factor binding protein-5 (IGFBP-5)-induced migration in mesangial cells, the roles of integrins and substrates were examined.

Levosimendan protects against experimental endotoxemic acute renal failure.

Endotoxemia induces a hemodynamic form of acute renal failure (ARF; renal vasoconstriction +/- reduced glomerular ultrafiltration coefficient, K(f); minimal/no histological damage). We tested whether levosimendan (LS), an ATP-sensitive K+ (K(ATP)) channel opener with cardiac ionotropic and possible anti-inflammatory properties, might have utility in combating this form of ARF. CD-1 mice were injected with LPS +/- LS.

IGF-1 induces rat glomerular mesangial cells to accumulate triglyceride.

Rat glomerular mesangial cells (MC) become lipid-laden foam cells when they are exposed to IGF-1. IGF-1 increased accumulation of triglyceride (TG) 2.5-fold in MC after 7 days.

Cellular lipid metabolism and the role of lipids in progressive renal disease.

Dyslipidemia contributes to the rate of progression of atherosclerosis and chronic kidney disease. Also, chronic kidney disease leads to the development of secondary abnormalities in lipid metabolism that contribute to increased cardiovascular morbidity and mortality. This review presents the mechanisms that underlie this risk.

Treatment of membranous nephropathy in the elderly.

MN is relatively common in the elderly and can lead to significant morbidity and mortality as a result of complications of the nephrotic syndrome and end-stage renal disease. Some cases of MN may be missed as asymptomatic urinary abnormalities and progressive renal disease may be attributed incorrectly to vascular disease or normal aging. Urinary abnormalities and changes in renal function should be evaluated in the elderly using the same criteria as applied in younger individuals.

Laminin-8/9 is synthesized by rat glomerular mesangial cells and is required for PDGF-induced mesangial cell migration.

Background: Laminin (LM), the major glycoprotein component of basement membranes is expressed as multiple isoforms in a developmentally regulated and tissue-specific manner. LM alpha4 has a limited tissue distribution and is highly expressed in the developing glomerulus. In the present study, we investigate the in vivo and in vitro expression and function of LM alpha4 in the glomerulus.

IGF-1-induced lipid accumulation impairs mesangial cell migration and contractile function.

Background: Chronic treatment of mesangial cells with insulin-like growth factor-1 (IGF-1) results in intracellular lipid accumulation. These mesangial cells resemble foam cells.

Methods: To determine whether this phenotype affects cell function, lipid-laden mesangial cells were tested for their ability to migrate in response to IGF-binding protein-5 (IGFBP-5) and to contract in response to angiotensin II (Ang II).

Synergistic activation of the rat laminin gamma1 chain promoter by the gut-enriched Kruppel-like factor (GKLF/KLF4) and Sp1.

Laminin is a multifunctional heterotrimeric protein present in extracellular matrix where it regulates processes that compose tissue architecture including cell differentiation. Laminin gamma1 is the most widely expressed laminin chain and its absence causes early lethality in mouse embryos. Laminin gamma1 chain gene (LAMC1) promoter contains several GC/GT-rich motifs including the bcn-1 element.

IGF-1 induces foam cell formation in rat glomerular mesangial cells.

When rat glomerular mesangial cells (MCs) are cultured with IGF-1 they accumulate intracellular lipid and take on foam cell morphology. These changes were characterized by electron microscopy and Nile red staining. To define the mechanism responsible for IGF-1-mediated lipid uptake, MCs were evaluated for endocytosis, scavenger receptor activity, and receptor-mediated uptake by the LDL receptor.

bcn-1 Element-dependent activation of the laminin gamma 1 chain gene by the cooperative action of transcription factor E3 (TFE3) and Smad proteins.

Laminin is a major component of the extracellular matrix. The laminin gamma1 chain is the least variant component of the laminin heterotrimeric assembly. The laminin gamma1 chain gene (LAMC1) expression is induced by several factors, including transforming growth factor-beta (TGF-beta).

A process for reducing workload and enhancing residents' education at an academic medical center.

Academic medical centers are under increasing pressure to find alternatives to residents for the provision of patient care and to expand and improve the educational opportunities for residents. To address these concerns, the authors performed a study of the medical wards at Harborview Medical Center, a county-owned medical center managed by the University of Washington School of Medicine. Admitting diagnoses, provider names, and billings were obtained from professional practice plan billing records.

Insulin alters heterogeneous nuclear ribonucleoprotein K protein binding to DNA and RNA.

The interaction of the multimodular heterogeneous nuclear ribonucleoprotein (hnRNP) K protein with many of its protein and nucleic acid partners is regulated by extracellular signals. Acting as a docking platform, K protein could link signal-transduction pathways to DNA- and RNA-directed processes such as transcription, mRNA processing, transport, and translation. Treatment of hepatocyte culture with insulin increased K protein tyrosine phosphorylation.

Lupus nephritis: lessons from experimental animal models.

Lupus nephritis is a frequent and severe complication of SLE. In the last decades, animal models for SLE have been studied widely to investigate the immunopathology of this autoimmune disease because abnormalities can be studied and manipulated before clinical signs of the disease become apparent. In this review an overview is given of our current knowledge on the development of lupus nephritis, as derived from animal models, and a hypothetical pathway for the development of lupus nephritis is postulated.