Vascular endothelial growth factor-C and -D are involved in lymphangiogenesis in mouse unilateral ureteral obstruction.

Lymphatic remodeling in inflammation has been found in tracheal mycoplasma infection, human kidney transplant, skin inflammation, peritonitis, and corneal inflammation. Here we investigated lymphangiogenesis in fibrotic area in unilateral ureteral obstruction, a model of progressive renal fibrosis, and evaluated the roles of vascular endothelial growth factor (VEGF)-C and -D in the obstructed kidney. Compared to sham-operated mice, the number of LYVE-1-positive lymphatic vessels, the proliferation of LYVE-1-positive lymphatic endothelial cells, along with VEGF-C and -D mRNA expression were all significantly increased following ureteral obstruction. Depletion of macrophages with clodronate decreased lymphangiogenesis in the obstructed kidney. VEGF-C expression was higher in M2- than in M1-polarized macrophages from bone marrow-derived macrophages, and also increased in Raw 264.7 or renal proximal tubule cells by stimulation with TGF-ß1 or TNF-α. VEGF-D reversed the inhibitory effect of TGF-ß1 on VEGF-C-induced migration, capillary-like tube formation, and proliferation of human lymphatic endothelial cells. Additionally, the blockade of VEGF-C and VEGF-D signaling decreased obstruction-induced lymphangiogenesis. Thus, VEGF-C and VEGF-D are associated with lymphangiogenesis in the fibrotic kidney in a mouse model of ureteral obstruction.

Proteomic analysis of wild-type and mutant huntingtin-associated proteins in mouse brains identifies unique interactions and involvement in protein synthesis.

Huntington disease is a neurodegenerative disorder caused by a CAG repeat amplification in the gene huntingtin (HTT) that is reflected by a polyglutamine expansion in the Htt protein. Nearly 20 years of research have uncovered roles for Htt in a wide range of cellular processes, and many of these discoveries stemmed from the identification of Htt-interacting proteins. However, no study has employed an impartial and comprehensive strategy to identify proteins that differentially associate with full-length wild-type and mutant Htt in brain tissue, the most relevant sample source to the disease condition. We analyzed Htt affinity-purified complexes from wild-type and HTT mutant juvenile mouse brain from two different biochemical fractions by tandem mass spectrometry. We compared variations in protein spectral counts relative to Htt to identify those proteins that are the most significantly contrasted between wild-type and mutant Htt purifications. Previously unreported Htt interactions with Myo5a, Prkra (PACT), Gnb2l1 (RACK1), Rps6, and Syt2 were confirmed by Western blot analysis. Gene Ontology analysis of these and other Htt-associated proteins revealed a statistically significant enrichment for proteins involved in translation among other categories. Furthermore, Htt co-sedimentation with polysomes in cytoplasmic mouse brain extracts is dependent upon the presence of intact ribosomes. Finally, wild-type or mutant Htt overexpression inhibits cap-dependent translation of a reporter mRNA in an in vitro system. Cumulatively, these data support a new role for Htt in translation and provide impetus for further study into the link between protein synthesis and Huntington disease pathogenesis.

A simple prediction score for kidney disease in the Korean population.

AIM: Screening algorithms for chronic kidney disease have been developed and validated in American populations. Given the worldwide burden of kidney disease, developing algorithms for populations outside the USA is needed. METHODS: Using simple, non-invasive questions, we developed a prediction model for chronic kidney disease from national population samples in Korea. The Korean National Health and Nutrition Examination Survey (n = 6565) was used for model development while validation was performed in two independent population samples, internal (n = 2921) and external datasets (n = 8166). Chronic kidney disease was defined as glomerular filtration rate < 60 mL/min per 1.73 m(2). RESULTS: Seven factors - age, female gender, anaemia, hypertension, diabetes mellitus, cardiovascular disease and proteinuria - were significantly associated with prevalent chronic kidney disease. Integer scores were assigned to variables based on the magnitude of associations: 2 for age 50-59 years, 3 for age 60-69 years and 4 for age 70 years or older, and 1 for female gender, anaemia, hypertension, diabetes, proteinuria and cardiovascular dis ase. Based on the Youden index, a value of 4 or greater defined a high risk population with sensitivity 89%, specificity 71%, and positive predictive value 19%, and negative predictive value 99%. The area under the curve was 0.83 for the development set, and 0.87 and 0.78 in the two validation datasets. CONCLUSION: This prediction algorithm, weighted towards common non-invasive variables, had good performance characteristics in an Asian population, and provides new evidence of the similarity of the algorithms for Western and Eastern populations.

Characterization of global yeast quantitative proteome data generated from the wild-type and glucose repression saccharomyces cerevisiae strains: the comparison of two quantitative methods.

The quantitative proteomic analysis of complex protein mixtures is emerging as a technically challenging but viable systems-level approach for studying cellular function. This study presents a large-scale comparative analysis of protein abundances from yeast protein lysates derived from both wild-type yeast and yeast strains lacking key components of the Snf1 kinase complex. Four different strains were grown under well-controlled chemostat conditions. Multidimensional protein identification technology followed by quantitation using either spectral counting or stable isotope labeling approaches was used to identify relative changes in the protein expression levels between the strains. A total of 2388 proteins were relatively quantified, and more than 350 proteins were found to have significantly different expression levels between the two strains of comparison when using the stable isotope labeling strategy. The stable isotope labeling based quantitative approach was found to be highly reproducible among biological replicates when complex protein mixtures containing small expression changes were analyzed. Where poor correlation between stable isotope labeling and spectral counting was found, the major reason behind the discrepancy was the lack of reproducible sampling for proteins with low spectral counts. The functional categorization of the relative protein expression differences that occur in Snf1-deficient strains uncovers a wide range of biological processes regulated by this important cellular kinase.

Relationship of plasma Dendroaspis natriuretic peptide-like immunoreactivity and echocardiographic parameters in chronic haemodialysis patients.

BACKGROUND AND AIMS: The Dendroaspis natriuretic peptide (DNP), which was recently isolated from the venom of the green Mamba snake, Dendroaspis angusticeps, is a 38 amino acid peptide containing a 17 amino acid disulfide ring structure. The purpose of this study was to evaluate the effect of haemodialysis (HD) on the plasma concentration of DNP, and to investigate the relationship between the 2-D echocardiographic parameters and the changes in the plasma DNP levels during HD. METHODS: Forty-five haemodialysis patients and 22 healthy individuals underwent a measurement of plasma DNP-like immunoreactivity, serum creatinine, haematocrit, blood pressure and bodyweight before and after each HD session. Echocardiography was performed before and after HD. The peak early diastolic transmitral flow velocity (E), peak late diastolic transmitral flow velocity (A), and E/A ratio were measured by using a pulsed Doppler echocardiogram. RESULTS: The plasma DNP-like immunoreactivity of those in the pre-HD state was significantly higher (235.6 +/- 45.8 pg/mL) than those of the healthy subjects (105.3 +/- 31.1 pg/mL). In addition, the plasma DNP-like immunoreactivity was significantly decreased after HD (204.4 +/- 55.4 pg/mL). The left atrial diameter, left ventricular diameter at end diastole and end systol, E velocity, A velocity, E/A ratio and inferior vena cava diameter were significantly decreased after HD. There were significant correlations between the changes of plasma DNP-like immunoreactivity and the changes in the bodyweight and inferior vena cava diameter, respectively. CONCLUSION: These results suggest that the plasma DNP-like immunoreactivity might be involved in the regulation of the blood volume in patients undergoing HD.

A case of unilateral renal cystic disease.

Unilateral renal cystic disease (URCD) is a distinct entity that is one of the renal cystic diseases. The clinical importance of URCD is to make a differential diagnosis from autosomal dominant polycystic kidney disease (ADPKD), multicystic dysplastic kidney, multilocular cystic renal neoplasm, and simple cysts. To confirm the diagnosis and to rule out asynchronous ADPKD requires long-term follow up, especially in younger patients.