Kanazawa Medical University

About: Kanazawa Medical University is a education organization based out in Kanazawa, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 3103 authors who have published 6322 publications receiving 144592 citations. The organization is also known as: Kanazawa ika daigaku.

Regulation of cell migration by sphingomyelin synthases: sphingomyelin in lipid rafts decreases responsiveness to signaling by the CXCL12/CXCR4 pathway.

Abstract: Sphingomyelin synthase (SMS) catalyzes the formation of sphingomyelin, a major component of the plasma membrane and lipid rafts. To investigate the role of SMS in cell signaling and migration induced by binding of the chemokine CXCL12 to CXCR4, we used mouse embryonic fibroblasts deficient in SMS1 and/or SMS2 and examined the effects of SMS deficiency on cell migration. SMS deficiency promoted cell migration through a CXCL12/CXCR4-dependent signaling pathway involving extracellular signal-regulated kinase (ERK) activation. In addition, SMS1/SMS2 double-knockout cells had heightened sensitivity to CXCL12, which was significantly suppressed upon transfection with the SMS1 or SMS2 gene or when they were treated with exogenous sphingomyelin but not when they were treated with the SMS substrate ceramide. Notably, SMS deficiency facilitated relocalization of CXCR4 to lipid rafts, which form platforms for the regulation and transduction of receptor-mediated signaling. Furthermore, we found that SMS deficiency potentiated CXCR4 dimerization, which is required for signal transduction. This dimerization was significantly repressed by sphingomyelin treatment. Collectively, our data indicate that SMS-derived sphingomyelin lowers responsiveness to CXCL12, thereby reducing migration induced by this chemokine. Our findings provide the first direct evidence for an involvement of SMS-generated sphingomyelin in the regulation of cell migration.

Nationwide multicentre kidney biopsy study of Japanese patients with type 2 diabetes

Abstract: Background The clinical and pathologic manifestations of nephropathy due to type 2 diabetes are diverse, but large-scale pathologic studies with long-term observations are limited. Methods Kidney biopsies and clinical data of 600 patients with type 2 diabetes were collected retrospectively from 13 centres across Japan. Thirteen pathologic findings (nine glomerular lesions, two interstitial lesions and two vascular lesions) were clearly defined and scored. Results During the observation period, there were 304 composite kidney events [dialysis, doubling of creatinine or reduction of estimated glomerular filtration rate (eGFR) by half], 31 instances of chronic kidney disease (CKD) G5D, 76 cardiovascular events and 73 deaths. The mean observation period was 72.4 months. The distribution of CKD heat map categories for the 600 patients was 103 green or yellow, 149 orange and 348 red. Even in the cases in the green and yellow category, diffuse lesions (81.6%), polar vasculosis (42.6%) and subendothelial space widening (35.1%) were commonly detected. Cox proportional hazard analysis revealed that the presence of nodular lesions [hazard ratio (HR) 21.1, 95% confidence interval (CI) 5.3-84.6], exudative lesions (HR 5.1, 95% CI 1.3-20.3) and mesangiolysis (HR 7.6, 95% CI 2.0-28.8) in cases in the green and yellow category were associated with significantly great impact on composite kidney events after adjustment for clinical risk factors. Conclusions This nationwide study on kidney biopsy of 600 cases with type 2 diabetes revealed that pathologic findings (presence of nodular lesions, exudative lesions and mesangiolysis) were strong predictors of kidney events in low-risk patients.

Hepatic venoconstriction is involved in anaphylactic hypotension in rats.

Abstract: We determined the roles of liver and splanchnic vascular bed in anaphylactic hypotension in anesthetized rats and the effects of anaphylaxis on hepatic vascular resistances and liver weight in isol...

Dipeptidyl peptidase-4 and kidney fibrosis in diabetes

Abstract: Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease worldwide and is associated with increased morbidity and mortality in patients with both type 1 and type 2 diabetes. Recent evidence revealed that dipeptidyl peptidase-4 (DPP-4) inhibitors may exhibit a protective effect against DN. In fact, the kidney is the organ where the DPP-4 activity is the highest level per organ weight. A preclinical analysis revealed that DPP-4 inhibitors also ameliorated kidney fibrosis. In this review, we analyzed recent reports in this field and explore the renoprotective effects and possible mechanism of the DPP-4 inhibitors.