ROCK2 regulates TGF- β-induced expression of CTGF and profibrotic genes via NF-κB and cytoskeleton dynamics in the mesangial cells.

ROCK2 regulates TGF-β-induced expression of CTGF and profibrotic genes via NF-κB and cytoskeleton dynamics in the mesangial cells. Am J Physiol Renal Physiol. 2019 Jul 31;: Authors: Nagai Y, Matoba K, Kawanami D, Takeda Y, Akamine T, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K, Nishimura R Abstract The small GTPase Rho and its effector Rho-kinase are involved in the pathogenesis of diabetic kidney disease. Rho-kinase has two isoforms, ROCK1 and ROCK2. However, it remains unclear which is mainly involved in the progression of diabetic glomerulosclerosis and the regulation of profibrotic mediators. Glomeruli isolated from type 2 diabetic db/db mice demonstrated increased gene expression of transforming growth factor β (TGF-β) and its downstream profibrotic mediators. Chemical inhibition of Rho-kinase suppressed the expression of profibrotic mediators in both isolated glomeruli and cultured mesangial cells. An investigation of mechanisms underlying this observation revealed activated Rho-kinase functions through the phosphorylation of JNK and Erk, and the nuclear translocation of nuclear factor-kappa B via actin dynamics. Knockdown by small interfering RNA against ROCK1 and ROCK2 showed that ROCK2 but not ROCK1 controls this fibrotic machinery. A further in vivo study showed that ROCK2 activity in the renal cortex of db/db mice was elevated compared to control db/m mice. Importantly, oral administration of ROCK2 inhibitor attenuated ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

Related Links:

This study aims to investigate the effects of the water extract of the flower of E. gardneri (WEE) on IR in palmitate (PA)-exposed HepG2 hepatocytes. WEE was characterized by UPLC analysis. PA-treated HepG2 cells were selected as the IR cell model. The cell viability was determined using MTT assay. Moreover, the glucose consumption and production were measured by glucose oxidase method. The glucose uptake and glycogen content were determined by the 2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose) glucose uptake assay and anthrone-sulfuric acid assay, respectively. The intracellular triglyceride conte...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Abstract Lacking sunlight exposure, northern latitudes, and dietary vitamin D insufficiency are co-prevalent with metabolic syndrome (MetS), type-2 diabetes (T2D), and non-alcoholic fatty liver diseases (NAFLD), implying potential causality and underlying mechanism. Whether vitamin D supplement or treatment can improve these disorders is controversial, due in part to absence of large-scale trials. Experimental investigation on the other hand uncovered novel biological functions of vitamin D in development, tumor suppression, and immune regulation, far beyond its original role as a vitamin in maintaining calcium ho...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research
Conclusion The gene regulatory effect of PKM2 is involved in renal inflammation in type 2 diabetic nephropathy by promoting the phosphorylation of STAT3 and NF-kB and the expression of intercellular adhesion molecule 1. Thus, the down-regulation of phosphorylated PKM2 may have protective effects against diabetic nephropathy by inhibiting renal inflammation. [...] © Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals: Table of contents  |  Abstract  |  Full text
Source: Experimental and Clinical Endocrinology and Diabetes - Category: Endocrinology Authors: Tags: Article Source Type: research
In conclusion, the present study suggested that inhibition of pygb prevents HG-induced cardiomyocyte apoptosis via Akt-HIF-α activation. PMID: 31905009 [PubMed - as supplied by publisher]
Source: Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Biochem Cell Biol Source Type: research
Publication date: Available online 22 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Oktawia Nilsson, Rita Del Giudice, Mototsugu Nagao, Caitriona Grönberg, Lena Eliasson, Jens O. LagerstedtAbstractThe increase of plasma levels of high-density lipoproteins and Apolipoprotein A-I (ApoA-I), its main protein component, has been shown to have a positive action on glucose disposal in type 2 diabetic patients. The current study investigates the unexplored function of ApoA-I to prime beta cells for improved insulin secretion.INS-1E rat clonal beta cells as well as isolated mur...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
Abstract Magnesium (in its ionized and biologically active form, Mg2+) is an essential trace element that participates in numerous physiologic processes. Abnormal Mg2+ homeostasis can lead to many metabolic disorders, including diabetes mellitus (DM) and its complications. Mg2+ participates in energy generation and is required for DNA and RNA synthesis, reproduction, and protein synthesis. Additionally, Mg2+ acts as a calcium antagonist and protects vascular endothelial cells from oxidative stress. Imbalances in Mg2+ status, more frequently hypomagnesemia, inhibit glucose transporter type 4 translocation, increase...
Source: Biological Trace Element Research - Category: Biology Authors: Tags: Biol Trace Elem Res Source Type: research
In this study, we hypothesized that moderately and chronically reducing ACh could attenuate the deleterious effects of aging on NMJs and skeletal muscles. To test this hypothesis, we analyzed NMJs and muscle fibers from heterozygous transgenic mice with reduced expression of the vesicular ACh transporter (VAChT), VKDHet mice, which present with approximately 30% less synaptic ACh compared to control mice. Because ACh is constitutively decreased in VKDHet, we first analyzed developing NMJs and muscle fibers. We found no obvious morphological or molecular differences between NMJs and muscle fibers of VKDHet and contro...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ConclusionsWe conclude that the β-adrenergic pathway is still functionally intact upon the inhibition of PI3Kα, showing that the activation of downstream insulin effectors is not required for the acute effects of β-adrenoceptor agonists on glucose homeostasis or thermogenesis.Graphical abstract
Source: Molecular Metabolism - Category: Endocrinology Source Type: research
ConclusionsWe conclude that the β-adrenergic pathway is still functionally intact upon the inhibition of PI3Kα, showing that the activation of downstream insulin effectors is not required for the acute effects of β-adrenoceptor agonists on glucose homeostasis or thermogenesis.
Source: Molecular Metabolism - Category: Endocrinology Source Type: research
In conclusion, our results showed that the pathophysiological factors in type 2 diabetes, including AGEs, were able to induce centrosome amplification. It is suggested that secreted Wnt6 binds to FZD4 to activate the canonical Wnt6 signaling pathway which is upstream of ROCK1 and 14-3-3σ, which is the cell signaling pathway underlying the diabetes-associated centrosome amplification. PMID: 31618077 [PubMed - as supplied by publisher]
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research
More News: Chemistry | Diabetes | Diabetes Type 2 | Endocrinology | Genetics | Glomeruli | Physiology | Study | Translocation | Urology & Nephrology