scholarly journals High glucose and TGF-β1 reduce expression of endoplasmic reticulum-resident selenoprotein S and selenoprotein N in human mesangial cells

Renal Failure ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 762-769
Author(s):  
Fumeng Huang ◽  
Yuanxu Guo ◽  
Li Wang ◽  
Lanmei Jing ◽  
Zhao Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
High Glucose ◽  
Mesangial Cells ◽  
Human Mesangial Cells ◽  
Selenoprotein S ◽  
Tgf Β1

scholarly journals Suppressor of cytokine signaling-1 reduces high glucose-induced TGF-β1 and fibronectin synthesis in human mesangial cells

FEBS Letters ◽  
2008 ◽  
Vol 582 (23-24) ◽  
pp. 3484-3488 ◽  
Author(s):  
Yonghong Shi ◽  
Yanling Zhang ◽  
Chen Wang ◽  
Chunyang Du ◽  
Song Zhao ◽  
...  
Keyword(s):  
High Glucose ◽  
Mesangial Cells ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Human Mesangial Cells ◽  
Tgf Β1

Klotho down-regulates Egr-1 by inhibiting TGF-β1/Smad3 signaling in high glucose treated human mesangial cells

2017 ◽  
Vol 487 (2) ◽  
pp. 216-222 ◽  
Author(s):  
Yang Li ◽  
Fang Hu ◽  
Meng Xue ◽  
Yi-Jie Jia ◽  
Zong-Ji Zheng ◽  
...  
Keyword(s):  
High Glucose ◽  
Mesangial Cells ◽  
Human Mesangial Cells ◽  
Tgf Β1

scholarly journals Thrombospondin-1 Is the Key Activator of TGF-β1 in Human Mesangial Cells Exposed to High Glucose

2001 ◽  
Vol 12 (4) ◽  
pp. 703-712 ◽  
Author(s):  
NATALIA YEVDOKIMOVA ◽  
NADIA ABDEL WAHAB ◽  
ROGER M. MASON
Keyword(s):  
Growth Factor ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Activation Mechanism ◽  
Plasminogen Activator Inhibitor 1 ◽  
Human Mesangial Cells ◽  
Thrombospondin 1 ◽  
Tgf Β1 ◽  
Pai 1

Abstract. Elevated levels of transforming growth factor-β1 (TGF-β1) are synthesized by human mesangial cells that are cultured in medium that contains high concentrations of glucose and mediate increased synthesis of fibronectin (FN), plasminogen activator inhibitor-1 (PAI-1), and changes in the expression of other genes. TGF-β1 is synthesized as a latent complex. Previous work indicated that high-glucose conditions also upregulate expression of thrombospondin-1 (TSP-1), a potential activator of latent TGF-β1. With the use of the synthetic peptide GGWSHW, an inhibitor of the TSP-1 activation mechanism, endogenous TSP-1 is shown to be responsible for converting high levels of latent TGF-β1 to bioactive growth factor over 3 wk of exposure of mesangial cells to 30 mM D-glucose. Peptide inhibition of TGF-β1 activation by TSP-1 in high-glucose conditions completely suppressed increases in FN and PAI-1 expression. Treating mesangial cells maintained in high glucose with a TSP-1 antisense oligonucleotide reduced TSP-1 expression to levels found in 4 mM D-glucose cultures, prevented TGF-β1 activation, and normalized expression of FN.

scholarly journals The Decorin High Glucose Response Element and Mechanism of Its Activation in Human Mesangial Cells

2000 ◽  
Vol 11 (9) ◽  
pp. 1607-1619 ◽  
Author(s):  
NADIA ABDEL WAHAB ◽  
SUSAN PARKER ◽  
JEAN-DANIEL SRAER ◽  
ROGER M. MASON
Keyword(s):  
Protein Kinase ◽  
High Glucose ◽  
Nuclear Translocation ◽  
Mesangial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Glucose Medium ◽  
Response Element ◽  
Human Mesangial Cells ◽  
Mitogen Activated Protein ◽  
Tgf Β1

Abstract. The decorin gene encodes a proteoglycan with putative structural and regulatory functions whose expression is markedly increased in human mesangial cells (HMC) exposed to high concentrations of glucose (15 to 30 mM). The gene has two promoters (P1 and P2) upstream of two alternative first exons. Transcripts driven by both promoters are present in HMC maintained in 4 mM D-glucose medium. After exposure to 30 mM D-glucose for 7 to 21 d, transcripts driven by P1 are markedly increased, whereas those driven by P2 decrease. Culture in 4 mM D-glucose medium containing transforming growth factor-β1 (TGF-β1) (1.25 ng/ml) has the same effect. However, addition of an excess of TGF-β neutralizing antibody to the 30 mM D-glucose cultures only partly suppressed increased decorin transcription from P1. In transformed HMC transfected with a reporter (p-SAEP) driven by P1 or P2, P1 activity increased twofold on treatment with either 30 mM D-glucose or TGF-β1 in 4 mM medium. P2 had little activity under any conditions. 5′ deletion of P1 showed that basal transcriptional activity lies within the proximal 378 bp, while the major high glucose and TGF-β response element is located in the -683 to -583-bp region. A putative cAMP response-like sequence (TGACGTTT) lies within this region. Electrophoretic mobility shift assays revealed the same pattern of multiple complexes between oligonucleotides containing this sequence and nuclear proteins extracted from HMC maintained in either 4 or 30 mM D-glucose conditions, but the latter were more prominent. cAMP response element binding protein (CREB) was identified as one transcription factor forming these complexes but other factors remain unidentified. Increased levels of phospho-(Ser 133) CREB were found in HMC exposed to 30 mM D-glucose. High glucose also activated and led to nuclear translocation of p42/44 mitogen-activated protein kinase and p38 mitogen-activated protein kinase, both of which can activate CREB by phosphorylation of serine 133.

scholarly journals Expression of extracellular matrix molecules in human mesangial cells in response to prolonged hyperglycaemia

1996 ◽  
Vol 316 (3) ◽  
pp. 985-992 ◽  
Author(s):  
Nadia Abdel WAHAB ◽  
Katherine HARPER ◽  
Roger M. MASON
Keyword(s):  
Cell Cultures ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Dermal Fibroblasts ◽  
Rt Pcr ◽  
Collagen Types ◽  
Human Mesangial Cells ◽  
Core Proteins ◽  
Cell Layers ◽  
Tgf Β1

Post-mitotic cultures of human mesangial cells were maintained in media containing 4–30 mM D-glucose for up to 28 days. Changes in mRNA and protein levels for specific macromolecules occurred between 7 and 14 days after initiating hyperglycaemic conditions. Slot blot analysis showed 2–3-fold increases in mRNAs for collagen type I, fibronectin, versican and perlecan, whereas mRNA for decorin was increased by up to 20-fold. Levels of mRNAs for biglycan and syndecan were unaffected by hyperglycaemic culture. Reverse transcriptase PCR (RT–PCR) confirmed that decorin mRNA levels are greatly elevated and also showed increased transcription of the TGF-β1 gene in hyperglycaemic cultures. Western analysis and ELISA indicated accumulations of collagen types I and III, laminin and fibronectin in the cell layers and media of hyperglycaemic cultures with increasing time. Type IV collagen did not accumulate in either compartment of hyperglycaemic mesangial cell cultures. Collagen types I, III, and fibronectin did not accumulate in the cell layers of hyperglycaemic human dermal fibroblasts, indicating a cell-specific response in mesangial cultures. Decorin and versican, but not biglycan, were increased in the hyperglycaemic mesangial cell culture media. There were no apparent changes in core proteins for decorin and biglycan in fibroblast media. Transforming growth factor β1 (TGF-β1) in hyperglycaemic mesangial cell cultures increased 5-fold after 7 days, but decreased thereafter to only approx. 2-fold after 28 days. The changes in TGF-β1 mRNA, as detected by RT–PCR, and protein followed one another closely.

scholarly journals Effects of Qijin granules on high glucose-induced proliferation, apoptosis and expression of nuclear factor- κB and MCP-1 in rat glomerular mesangial cells

2021 ◽  
Vol 20 (9) ◽  
pp. 1819-1826
Author(s):  
Yuanfeng Yang ◽  
Gaocai Xiong ◽  
Renhui Yang ◽  
Yuchuan Li ◽  
Yuling Luo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
High Glucose ◽  
Mesangial Cells ◽  
Control Group ◽  
Glomerular Mesangial Cells ◽  
Smad Signaling ◽  
Apoptosis Rate ◽  
Proliferation And Apoptosis ◽  
Protein Expressions ◽  
Tgf Β1

Purpose: To investigate the effects of Qijin granules on high glucose-induced proliferation and apoptosis in rat glomerular mesangial cells (MC).Methods: MC cells from rats were passaged and cultured, and randomly divided into control group (CNG), high glucose group (HGG), Western medicine group (WMG, high glucose + Benazepril + Gliquidone), and Qijin granules 1/2/3 group (high glucose + different doses of Qijin granules). Mesangial cells proliferation was measured using MTT assay. The NF-κB, MCP-1 and inflammatory factors in supernatant were determined by ELISA. Apoptosis rate and cell cycle were assessed by flow cytometry. The apoptosis-related TGF-β1/Smad signaling pathway-related protein expressions were measured by Western blot.Results: The A-value and early apoptosis rate, apoptosis rate and S-phase percentage, and protein expressions of NF-κB, MCP-1, IL-6, IL-2, TNF-ɑ, Bax, Cyt-C, caspase-3, TGF-β1, and p-Smad3 of MC cells in the HGG at 12 h, 24 h and 48 h were higher than those in the CNG. The above indices were lower in the WMG, and Qijin granules 1/2/3 groups than in the HGG. The Bcl-2, Smad7 protein expression level and the percentage of G1 and G2/M phase were lower in the HGG than in the CNG, and the above indeices were higher in the WMG and Qijin granules 1/2/3 group than in HGG.Conclusion: Qijin granules can dose-dependently inhibit high glucose-induced proliferation and apoptosis in rat MC cells, block the cell cycle and reduce inflammatory responses. This may be related to the regulation of NF-κB, MCP-1 and TGF-β1/Smad signaling pathways. These findings provide theoretical and experimental basis for the clinical treatment of early diabetic nephropathy.

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