scholarly journals High glucose induces platelet-derived growth factor-C via carbohydrate response element-binding protein in glomerular mesangial cells

2016 ◽  
Vol 4 (6) ◽  
pp. e12730 ◽  
Author(s):  
Hiroya Kitsunai ◽  
Yuichi Makino ◽  
Hidemitsu Sakagami ◽  
Katsutoshi Mizumoto ◽  
Tsuyoshi Yanagimachi ◽  
...  
Keyword(s):  
Growth Factor ◽  
High Glucose ◽  
Mesangial Cells ◽  
Binding Protein ◽  
Platelet Derived Growth Factor ◽  
Glomerular Mesangial Cells ◽  
Response Element ◽  
Element Binding Protein ◽  
Factor C

scholarly journals High glucose activates HIF-1-mediated signal transduction in glomerular mesangial cells through a carbohydrate response element binding protein

2010 ◽  
Vol 78 (1) ◽  
pp. 48-59 ◽  
Author(s):  
Tsubasa Isoe ◽  
Yuichi Makino ◽  
Katsutoshi Mizumoto ◽  
Hidemitsu Sakagami ◽  
Yukihiro Fujita ◽  
...  
Keyword(s):  
Signal Transduction ◽  
High Glucose ◽  
Mesangial Cells ◽  
Binding Protein ◽  
Glomerular Mesangial Cells ◽  
Response Element ◽  
Element Binding Protein

scholarly journals Carbohydrate response element binding protein (ChREBP) modulates the inflammatory response of mesangial cells in response to glucose

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yan Chen ◽  
Yan-Jun Wang ◽  
Ying Zhao ◽  
Jin-Cheng Wang
Keyword(s):  
Diabetes Mellitus ◽  
Inflammatory Response ◽  
Mesangial Cells ◽  
Binding Protein ◽  
The Body ◽  
Mrna Levels ◽  
Diabetic Mice ◽  
Response Element ◽  
Tnf Α ◽  
Element Binding Protein

Diabetic nephropathy (DN) is one of the most devastating complications of diabetes mellitus. Carbohydrate response element binding protein (ChREBP) is a basic helix–loop–helix leucine zipper transcription factor that primarily mediates glucose homeostasis in the body. The present study investigated the role of ChREBP in the pathogenesis of DN. The expression of ChREBP was detected in patients with type 2 diabetes mellitus (T2DM), diabetic mice, and mesangial cells. ELISA was used to measure cytokine production in mesangial cells. Flow cytometry analysis was performed to detect the apoptosis of mesangial cells in the presence of high glucose. The expression levels of ChREBP and several cytokines (TNF-α, IL-1β, and IL-6) were up-regulated in T2DM patients. The mRNA and protein levels of ChREBP were also significantly elevated in the kidneys of diabetic mice. Moreover, glucose treatment promoted mRNA levels of TNF-α, IL-1β, and IL-6 in mesangial cells. Glucose stimulation induced significant apoptosis of SV40 MES 13 cells. In addition, transfection with ChREBP siRNA significantly inhibited ChREBP expression. Consequently, the inflammatory responses and apoptosis were inhibited in SV40 MES 13 cells. These results demonstrated that ChREBP could mediate the inflammatory response and apoptosis of mesangial cells, suggesting that ChREBP may be involved in the pathogenesis of DN.

scholarly journals Role for carbohydrate response element-binding protein (ChREBP) in high glucose-mediated repression of long noncoding RNA Tug1

2020 ◽  
Vol 295 (47) ◽  
pp. 15840-15852
Author(s):  
Jianyin Long ◽  
Daniel L. Galvan ◽  
Koki Mise ◽  
Yashpal S. Kanwar ◽  
Li Li ◽  
...  
Keyword(s):  
High Glucose ◽  
Noncoding Rna ◽  
Binding Protein ◽  
Biological Activities ◽  
Response Element ◽  
Histone Deacetylase 1 ◽  
Glucose Levels ◽  
Expression Studies ◽  
Element Binding Protein ◽  
Lncrna Tug1

Long noncoding RNAs (lncRNAs) have been shown to play key roles in a variety of biological activities of the cell. However, less is known about how lncRNAs respond to environmental cues and what transcriptional mechanisms regulate their expression. Studies from our laboratory have shown that the lncRNA Tug1 (taurine upregulated gene 1) is crucial for the progression of diabetic kidney disease, a major microvascular complication of diabetes. Using a combination of proximity labeling with the engineered soybean ascorbate peroxidase (APEX2), ChIP-qPCR, biotin-labeled oligonucleotide pulldown, and classical promoter luciferase assays in kidney podocytes, we extend our initial observations in the current study and now provide a detailed analysis on a how high-glucose milieu downregulates Tug1 expression in podocytes. Our results revealed an essential role for the transcription factor carbohydrate response element binding protein (ChREBP) in controlling Tug1 transcription in the podocytes in response to increased glucose levels. Along with ChREBP, other coregulators, including MAX dimerization protein (MLX), MAX dimerization protein 1 (MXD1), and histone deacetylase 1 (HDAC1), were enriched at the Tug1 promoter under high-glucose conditions. These observations provide the first characterization of the mouse Tug1 promoter's response to the high-glucose milieu. Our findings illustrate a molecular mechanism by which ChREBP can coordinate glucose homeostasis with the expression of the lncRNA Tug1 and further our understanding of dynamic transcriptional regulation of lncRNAs in a disease state.

scholarly journals Regulation of Rat Mesangial Cell Migration by Platelet-Derived Growth Factor, Angiotensin II, and Adrenomedullin

1999 ◽  
Vol 10 (12) ◽  
pp. 2495-2502 ◽  
Author(s):  
MASAKAZU KOHNO ◽  
KENICHI YASUNARI ◽  
MIEKO MINAMI ◽  
HIROAKI KANO ◽  
KENSAKU MAEDA ◽  
...  
Keyword(s):  
Cell Migration ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Inhibitory Effect ◽  
Platelet Derived Growth Factor ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Concentration Dependent Manner

Abstract. This study sought to determine whether platelet-derived growth factor (PDGF) and angiotensin II (AngII) stimulate migration of cultured rat glomerular mesangial cells. After finding that this was so, the effects of adrenomedullin (ADM) and cAMP-elevating agents on basal and stimulated mesangial cell migration were examined. Two isoforms of PDGF, AB and BB, stimulated migration in a concentration-dependent manner between 1 and 50 ng/ml, while the AA isoform lacked significant effect. AngII modestly but significantly stimulated migration in a concentration-dependent manner between 10-7 and 10-6 mol/L. Rat ADM significantly inhibited the PDGF BB- and AngII-stimulated migration in a concentration-dependent manner between 10-8 and 10-7 mol/L. Inhibition by rat ADM was accompanied by an increase in cellular cAMP. cAMP agonists or inducers such as 8-bromo cAMP, forskolin, and prostaglandin I2 also significantly reduced the stimulated migration. H 89, a protein kinase A (PKA) inhibitor, attenuated the inhibitory effect of ADM, and a calcitonin gene-related peptide (CGRP) receptor antagonist, human CGRP (8-37), abolished the inhibitory effects of rat ADM. These results suggest that PDGF AB and BB as well as AngII stimulate rat mesangial cell migration and that ADM can inhibit PDGF BB- and AngII-stimulated migration, at least in part through cAMP-dependent mechanisms likely to involve specific ADM receptors with which CGRP interacts. The adenylate cyclase/cAMP/PKA system may be involved in the migration-inhibitory effect of ADM in these cells.

Ca(2+)-permeable channel associated with platelet-derived growth factor receptor in mesangial cells

1994 ◽  
Vol 267 (2) ◽  
pp. C456-C465 ◽  
Author(s):  
H. Matsunaga ◽  
B. N. Ling ◽  
D. C. Eaton
Keyword(s):  
Growth Factor ◽  
Mesangial Cells ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Glomerular Mesangial Cells ◽  
Open Probability ◽  
Permeable Channel ◽  
Close Proximity ◽  
Voltage Dependent ◽  
Inside Out

We used patch-clamp methods to study the effect of platelet-derived growth factor (PDGF) on Ca2+ entry in cultured rat glomerular mesangial cells. In cell-attached patches, application of 50 ng/ml PDGF-BB inside, but not outside, the pipette frequently induced channel openings. The unitary conductance was 0.67 +/- 0.09 pS (n = 8) with 110 mM Mn2+ and 1.03 +/- 0.19 pS (n = 11) with 110 mM Ca2+ as the charge carrier. Number of channels times open probability was 0.515 +/- 0.144 (n = 14) with intrapipette PDGF and 0.037 +/- 0.022 (n = 12) without. Channel kinetics were only slightly voltage dependent. There was no effect of replacing chloride with gluconate in excised inside-out patches, showing that the channel was cation selective. The permeability (P) ratio for PMn/PNa was 1.65 and for PCa/PNa was 1.24. With the use of amphotericin B " perforated" whole cell patches, PDGF induced a small inward current (-16.1 +/- 4.33 pA; n = 11, membrane potential = -70 mV) consistent with 3,000-4,000 channels/cell. In summary, we have described a very-low-conductance Ca(2+)-permeable channel in rat mesangial cells with the following properties. 1) Activation by PDGF-BB occurs only when applied in close proximity to the channel. 2) Once activated, open probability is only slightly voltage dependent. 3) Under normal circumstances, the channel would probably appear to be cation nonselective, but with a permeability to divalent more than monovalent cations. 4) This PDGF-induced channel could provide a ligand-gated pathway for Ca2+ entry into mesangial cells that does not require membrane depolarization.

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