scholarly journals Tanshinone IIA Inhibits High Glucose-Induced Collagen Synthesis via Nuclear Factor Erythroid 2-Related Factor 2 in Cardiac Fibroblasts

2018 ◽  
Vol 51 (5) ◽  
pp. 2250-2261 ◽  
Author(s):  
Yi-Ting  Tsai ◽  
Shih-Hurng Loh ◽  
Chung-Yi Lee ◽  
Shiao-Ping Lee ◽  
Yen-Lin Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
High Glucose ◽  
Collagen Synthesis ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Tanshinone Iia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Related Factor ◽  
Nuclear Factor ◽  
Tgf Β1

Background/Aims: Diabetes is associated with increased incidence of myocardial dysfunction, which is partly characterized by interstitial and perivascular fibrosis. Cardiac fibroblasts have been identified as an important participant in the development of cardiac fibrosis. Exposure of cultured cardiac fibroblasts to high glucose resulted in increased collagen synthesis. Tanshinone IIA can alleviate the ventricular fibrosis that develops in a number of different experimental conditions. However, whether tanshinone IIA can prevent high glucose-induced collagen synthesis in cardiac fibroblasts remains unknown. The aim of this study was to evaluate the effects of tanshinone IIA on high glucose-induced collagen synthesis in cardiac fibroblasts. Methods: Rat cardiac fibroblasts were cultured in high glucose (25 mM) media in the absence or presence of tanshinone IIA and the changes in collagen synthesis, transforming growth factor-β1 (TGF-β1) production and related signaling molecules were assessed by 3H-proline incorporation, quantitative polymerase chain reaction, enzyme linked immunosorbent assay, and Western blotting. Results: The results indicate cardiac fibroblasts exposed to high glucose condition show increased cell proliferation and collagen synthesis and these effects were abolished by tanshinone IIA treatment. Furthermore, the inhibitory effect of tanshinone IIA on high glucose induced cell proliferation and collagen synthesis may be associated with its activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and the inhibition of TGF-β1 production and Smad2/3 phosphorylation. Conclusion: In summary, our results highlights the critical role tanshinone IIA plays as an antioxidant in attenuating high glucose-mediated collagen synthesis through inhibiting TGF-β1/Smad signaling in cardiac fibroblasts which provide a mechanistic basis for the clinical application of tanshinone IIA in the treating diabetic-related cardiac fibrosis.

scholarly journals Cafestol Inhibits High-Glucose-Induced Cardiac Fibrosis in Cardiac Fibroblasts and Type 1-Like Diabetic Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ju-Chi Liu ◽  
Po-Yuan Chen ◽  
Wen-Rui Hao ◽  
Yi-Chung Liu ◽  
Ping-Chiang Lyu ◽  
...  
Keyword(s):  
High Glucose ◽  
Collagen Synthesis ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Biological Effects ◽  
Diabetic Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Tgf Β1

Diabetes is associated with the development of myocardial fibrosis, which is related to various cardiac diseases. Cafestol, one of the active ingredients in coffee, has been reported to exert biological effects. However, whether cafestol can ameliorate diabetes-induced cardiac fibrosis remains unknown. The aim of this study was to evaluate the effects of cafestol on cardiac fibrosis in high-glucose-treated cardiac fibroblasts and streptozocin- (STZ-) induced diabetic rats. Rat cardiac fibroblasts were cultured in high-glucose (25 mM) media in the absence or presence of cafestol, and the changes in collagen synthesis, transforming growth factor-β1 (TGF-β1) production, and related signaling molecules were assessed on the basis of 3H-proline incorporation, enzyme-linked immunosorbent assay, and western blotting. Cardiac fibroblasts exposed to high-glucose conditions exhibited increased collagen synthesis, TGF-β1 production, and Smad2/3 phosphorylation, and these effects were mitigated by cafestol treatment. Furthermore, cafestol increased the translocation of nuclear factor erythroid 2-related factor 2 and increased the expression of heme oxygenase-1. The results of molecular docking analysis suggested a selective interaction of cafestol with Kelch-like ECH-associated protein 1. The rats with untreated STZ-induced diabetes exhibited considerable collagen accumulation, which was ameliorated by cafestol. Moreover, activities of catalase, superoxide dismutase, general matrix metalloproteinase, and reduced glutathione concentration were upregulated, whereas malondialdehyde level was downregulated by treatment with cafestol in rats with cardiac fibrosis. These findings highlight the effects of cafestol, which may be useful in treating diabetes-related cardiac fibrosis.

scholarly journals Role for high-glucose-induced protein O-GlcNAcylation in stimulating cardiac fibroblast collagen synthesis

2014 ◽  
Vol 306 (9) ◽  
pp. C794-C804 ◽  
Author(s):  
Hugo Aguilar ◽  
Eduardo Fricovsky ◽  
Sang Ihm ◽  
Magdalena Schimke ◽  
Lisandro Maya-Ramos ◽  
...  
Keyword(s):  
High Glucose ◽  
Collagen Synthesis ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Transforming Growth Factor Β1 ◽  
Protein Levels ◽  
Normal Glucose ◽  
Arginase Ii ◽  
Tgf Β1

Excess enzyme-mediated protein O-GlcNAcylation is known to occur with diabetes mellitus. A characteristic of diabetic cardiomyopathy is the development of myocardial fibrosis. The role that enhanced protein O-GlcNAcylation plays in modulating the phenotype of cardiac fibroblasts (CF) is unknown. To address this issue, rat CF were cultured in normal glucose (NG; 5 mM glucose) or high-glucose (HG; 25 mM) media for 48 h. Results demonstrate that CF cultured in HG have higher levels (∼50%) of overall protein O-GlcNAcylation vs. NG cells. Key regulators of collagen synthesis such as transforming-growth factor-β1 (TGF-β1), SMADs 2/3, and SMAD 7 protein levels, including those of arginase I and II, were altered, leading to increases in collagen levels. The nuclear transcription factor Sp1 and arginase II evidence excess O-GlcNAcylation in HG cells. Expression in CF of an adenovirus coding for the enzyme N-acetylglucosaminidase, which removes O-GlcNAc moieties from proteins, decreased Sp1 and arginase II O-GlcNAcylation and restored HG-induced perturbations in CF back to NG levels. These findings may have important pathophysiological implications for the development of diabetes-induced cardiac fibrosis.

scholarly journals Inhibitory Effects of Momordicine I on High-Glucose-Induced Cell Proliferation and Collagen Synthesis in Rat Cardiac Fibroblasts

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Po-Yuan Chen ◽  
Neng-Lang Shih ◽  
Wen-Rui Hao ◽  
Chun-Chao Chen ◽  
Ju-Chi Liu ◽  
...  
Keyword(s):  
High Glucose ◽  
Collagen Synthesis ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Critical Role ◽  
Inhibitory Effect ◽  
Related Factor ◽  
Fibroblast Proliferation ◽  
Fibroblast Activation

Diabetes-associated cardiac fibrosis is a severe cardiovascular complication. Momordicine I, a bioactive triterpenoid isolated from bitter melon, has been demonstrated to have antidiabetic properties. This study investigated the effects of momordicine I on high-glucose-induced cardiac fibroblast activation. Rat cardiac fibroblasts were cultured in a high-glucose (25 mM) medium in the absence or presence of momordicine I, and the changes in collagen synthesis, transforming growth factor-β1 (TGF-β1) production, and related signaling molecules were assessed. Increased oxidative stress plays a critical role in the development of high-glucose-induced cardiac fibrosis; we further explored momordicine I’s antioxidant activity and its effect on fibroblasts. Our data revealed that a high-glucose condition promoted fibroblast proliferation and collagen synthesis and these effects were abolished by momordicine I (0.3 and 1 μM) pretreatment. Furthermore, the inhibitory effect of momordicine I on high-glucose-induced fibroblast activation may be associated with its activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the inhibition of reactive oxygen species formation, TGF-β1 production, and Smad2/3 phosphorylation. The addition of brusatol (a selective inhibitor of Nrf2) or Nrf2 siRNA significantly abolished the inhibitory effect of momordicine I on fibroblast activation. Our findings revealed that the antifibrotic effect of momordicine I was mediated, at least partially, by the inhibition of the TGF-β1/Smad pathway, fibroblast proliferation, and collagen synthesis through Nrf2 activation. Thus, this work provides crucial insights into the molecular pathways for the clinical application of momordicine I for treating diabetes-associated cardiac fibrosis.

scholarly journals Neferine inhibits proliferation and collagen synthesis induced by high glucose in cardiac fibroblasts and reduces cardiac fibrosis in diabetic mice

Oncotarget ◽  
2016 ◽  
Vol 7 (38) ◽  
pp. 61703-61715 ◽  
Author(s):  
Xue Liu ◽  
Xiuhui Song ◽  
Jianjun Lu ◽  
Xueying Chen ◽  
Ershun Liang ◽  
...  
Keyword(s):  
High Glucose ◽  
Collagen Synthesis ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Diabetic Mice

scholarly journals High Glucose Activated Cardiac Fibroblasts by a Disruption of Mitochondria-Associated Membranes

2021 ◽  
Vol 12 ◽  
Author(s):  
Ling-Yu Zhang ◽  
Rui-Ting Lin ◽  
Hao-Ran Chen ◽  
Yong-Cong Yang ◽  
Meng-Fei Lin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mitochondrial Respiration ◽  
High Glucose ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Mitofusin 2 ◽  
Atp Production ◽  
Proliferation And Apoptosis

Cardiac fibrosis is evident even in the situation without a significant cardiomyocyte loss in diabetic cardiomyopathy and a high glucose (HG) level independently activates the cardiac fibroblasts (CFs) and promotes cell proliferation. Mitochondrial respiration and glycolysis, which are key for cell proliferation and the mitochondria-associated membranes (MAMs), are critically involved in this process. However, the roles and the underlying mechanism of MAMs in the proliferation of HG-induced CFs are largely unknown. The proliferation and apoptosis of CFs responding to HG treatment were evaluated. The MAMs were quantified, and the mitochondrial respiration and cellular glycolytic levels were determined using the Seahorse XF analyzer. The changes of signal transducer and activator of transcription 3 (STAT3) and mitofusin-2 (MFN2) in responding to HG were also determined, the effects of which on cell proliferation, MAMs, and mitochondrial respiration were assessed. The effects of STAT3 on MFN2 transcription was determined by the dual-luciferase reporter assay (DLRA) and chromatin immunoprecipitation (CHIP). HG-induced CFs proliferation increased the glycolytic levels and adenosine triphosphate (ATP) production, while mitochondrial respiration was inhibited. The MAMs and MFN2 expressions were significantly reduced on the HG treatment, and the restoration of MFN2 expression counteracted the effects of HG on cell proliferation, mitochondrial respiration of the MAMs, glycolytic levels, and ATP production. The mitochondrial STAT3 contents were not changed by HG, but the levels of phosphorylated STAT3 and nuclear STAT3 were increased. The inhibition of STAT3 reversed the reduction of MFN2 levels induced by HG. The DLRA and CHIP directly demonstrated the negative regulation of MFN2 by STAT3 at the transcription levels via interacting with the sequences in the MFN2 promoter region locating at about −400 bp counting from the start site of transcription. The present study demonstrated that the HG independently induced CFs proliferation via promoting STAT3 translocation to the nucleus, which switched the mitochondrial respiration to glycolysis to produce ATP by inhibiting MAMs in an MFN2-depression manner.

scholarly journals Corrigendum to “Inhibitory Effects of Momordicine I on High-Glucose-Induced Cell Proliferation and Collagen Synthesis in Rat Cardiac Fibroblasts”

2019 ◽  
Vol 2019 ◽  
pp. 1-1
Author(s):  
Po-Yuan Chen ◽  
Neng-Lang Shih ◽  
Wen-Rui Hao ◽  
Chun-Chao Chen ◽  
Ju-Chi Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
High Glucose ◽  
Collagen Synthesis ◽  
Cardiac Fibroblasts ◽  
Inhibitory Effects

scholarly journals Tanshinone IIA Improves Ventricular Remodeling following Cardiac Infarction by Regulating miR-205-3p

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Peng Qiao ◽  
Jie Xu ◽  
Xueni Liu ◽  
Xuehan Li
Keyword(s):  
Cardiac Fibrosis ◽  
Rna Binding ◽  
Ventricular Remodeling ◽  
Cardiac Fibroblasts ◽  
Left Ventricular ◽  
Tanshinone Iia ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Tgf Β1

Objective. To illustrate the role of tanshinone IIA (TSN) in regulating cardiac structure and function following myocardial infarction (MI) and the involvement of miR-205-3p in TSN-induced antifibrosis effect on ventricular remodeling. Patients and Methods. One hundred MI patients were randomly assigned into two groups, and they were treated with TSN (TSN group, n = 50 ) or conventional therapy (control group, n = 50 ). Plasma levels of miR-205-3p and TGF-β1 were detected in each patient. Echocardiography was conducted in each patient at post-MI 1 day, 2 weeks, and 4 weeks, respectively, for recording LVIDd (left ventricular internal-diastolic diameter), LVIDs (left ventricular internal-systolic diameter), and LVEF (left ventricular ejection fraction). The interaction between miR-205-3p and TGF-β1 was examined by the RNA-Binding Protein Immunoprecipitation (RIP) assay. After induction of TGF-β1 and/or 10 μL of TSN in cardiac fibroblasts, relative levels of miR-205-3p, Col1a1, and Col3a1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Results. Compared with the control group, miR-205-3p and TGF-β1 were downregulated in plasma of MI patients in the TSN group. In the TSN group, LVIDd and LVIDs were reduced, and EF was enhanced at 2 weeks and 4 weeks compared with that at post-MI 1 day. miR-205-3p could negatively interact with TGF-β1. TSN induction abolished the regulatory effects of TGF-β1 on downregulating miR-205-3p and upregulating Col1a1 and Col3a1 in cardiac fibroblasts. Conclusions. Through upregulating miR-205-3p and downregulating TGF-β1, TSN alleviates cardiac fibrosis and improves ventricular remodeling following MI.

scholarly journals Camu-Camu Fruit Extract Inhibits Oxidative Stress and Inflammatory Responses by Regulating NFAT and Nrf2 Signaling Pathways in High Glucose-Induced Human Keratinocytes

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3174
Author(s):  
Nhung Quynh Do ◽  
Shengdao Zheng ◽  
Bom Park ◽  
Quynh T. N. Nguyen ◽  
Bo-Ram Choi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
High Glucose ◽  
Skin Diseases ◽  
Inflammatory Responses ◽  
Human Keratinocytes ◽  
Related Factor ◽  
Nuclear Factor ◽  
Fruit Extract ◽  
Activated T Cells

Myrciaria dubia (HBK) McVaugh (camu-camu) belongs to the family Myrtaceae. Although camu-camu has received a great deal of attention for its potential pharmacological activities, there is little information on the anti-oxidative stress and anti-inflammatory effects of camu-camu fruit in skin diseases. In the present study, we investigated the preventative effect of 70% ethanol camu-camu fruit extract against high glucose-induced human keratinocytes. High glucose-induced overproduction of reactive oxygen species (ROS) was inhibited by camu-camu fruit treatment. In response to ROS reduction, camu-camu fruit modulated the mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NFAT) signaling pathways related to inflammation by downregulating the expression of proinflammatory cytokines and chemokines. Furthermore, camu-camu fruit treatment activated the expression of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased the NAD(P)H:quinone oxidoreductase1 (NQO1) expression to protect keratinocytes against high-glucose-induced oxidative stress. These results indicate that camu-camu fruit is a promising material for preventing oxidative stress and skin inflammation induced by high glucose level.

Tanshinone IIA Inhibits Angiotensin II-Induced Cell Proliferation in Rat Cardiac Fibroblasts

2011 ◽  
Vol 39 (02) ◽  
pp. 381-394 ◽  
Author(s):  
Paul Chan ◽  
Ju-Chi Liu ◽  
Li-Jen Lin ◽  
Po-Yuan Chen ◽  
Tzu-Hurng Cheng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
Angiotensin Ii ◽  
Cardiac Fibroblasts ◽  
Tanshinone Iia ◽  
No Production ◽  
Ang Ii ◽  
Erk Phosphorylation ◽  
Enos Phosphorylation ◽  
Ros Formation

Tanshinone IIA extracted from Danshen, a popular medicinal herb used in traditional Chinese medicine, exhibits cardio-protective effects. However, the mechanism of its cardioprotective effect is not well established. The aims of this study were to examine whether tanshinone IIA may alter angiotensin II (Ang II)-induced cell proliferation and to identify the putative underlying signaling pathways in rat cardiac fibroblasts. Cultured rat cardiac fibroblasts were pre-treated with tanshinone IIA and stimulated with Ang II, cell proliferation and endothelin-1 (ET-1) expression were examined. The effect of tanshinone IIA on Ang II-induced reactive oxygen species (ROS) formation, and extracellular signal-regulated kinase (ERK) phosphorylation were also examined. In addition, the effect of tanshinone IIA on nitric oxide (NO) production, and endothelial nitric oxide synthase (eNOS) phosphorylation were tested to elucidate the intracellular mechanism. The increased cell proliferation and ET-1 expression by Ang II (100 nM) were partially inhibited by tanshinone IIA. Tanshinone IIA also inhibited Ang II-increased ROS formation, and ERK phosphorylation. In addition, tanshinone IIA was found to increase the NO generation, and eNOS phosphorylation. NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, and the short interfering RNA transfection for eNOS markedly attenuated the inhibitory effect of tanshinone IIA on Ang II-induced cell proliferation. The results suggest that tanshinone IIA prevents cardiac fibroblast proliferation by interfering with the generation of ROS and involves the activation of the eNOS-NO pathway.

Urotensin-2 promotes collagen synthesis via ERK1/2-dependent and ERK1/2-independent TGF-β1 in neonatal cardiac fibroblasts

2011 ◽  
Vol 35 (2) ◽  
pp. 93-98 ◽  
Author(s):  
Hong‑Yan Dai ◽  
Tao He ◽  
Xiao‑Lu Li ◽  
Wen‑Liang Xu ◽  
Zhi‑Ming Ge
Keyword(s):  
Collagen Synthesis ◽  
Cardiac Fibroblasts ◽  
Tgf Β1
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