High glucose promotes the production of collagen types I and III by cardiac fibroblasts through a pathway dependent on extracellular-signal-regulated kinase 1/2

Tang, Mengxiong; Zhang, Wei; Lin, Haiyan; Jiang, Hong; Dai, Hongji; Zhang, Yun

doi:10.1007/s11010-006-9401-6

Cited by 64 publications

(57 citation statements)

References 25 publications

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“…mesangial cells, and vascular smooth muscle cells contribute to the cardiovascular and nephritic complications of diabetes (Neumann et al 2002, Tokudome et al 2004, Maile et al 2010, and ERK1/2 activation has been linked to high glucose-induced fibrosis (Tang et al 2007). Consistent with these previous reports, high glucose presently increased cell proliferation and affected the expression of ECM-related genes in cardiac fibroblasts by modulating ERK activities.…”

Section: Discussionsupporting

confidence: 78%

IGFBP5 mediates high glucose-induced cardiac fibroblast activation

Song¹,

Kim²,

Kim³

et al. 2013

Journal of Molecular Endocrinology

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This study examined whether IGF-binding protein 5 (IGFBP5) is involved in the high glucoseinduced deteriorating effects in cardiac cells. Cardiac fibroblasts and cardiomyocytes were isolated from the hearts of 1-to 3-day-old Sprague Dawley rats. Treatment of fibroblasts with 25 mM glucose increased the number of cells and the mRNA levels of collagen III, matrix metalloproteinase 2 (MMP2), and MMP9. High glucose increased ERK1/2 activity, and the ERK1/2 inhibitor PD98059 suppressed high glucose-mediated fibroblast proliferation and increased collagen III mRNA levels. Whereas high glucose increased both mRNA and protein levels of IGFBP5 in fibroblasts, high glucose did not affect IGFBP5 protein levels in cardiomyocytes. The high glucose-induced increase in IGFBP5 protein levels was inhibited by PD98059 in fibroblasts. While recombinant IGFBP5 increased ERK phosphorylation, cell proliferation, and the mRNA levels of collagen III, MMP2, and MMP9 in fibroblasts, IGFBP5 increased c-Jun N-terminal kinase phosphorylation and induced apoptosis in cardiomyocytes. The knockdown of IGFBP5 inhibited high glucose-induced cell proliferation and collagen III mRNA levels in fibroblasts. Although high glucose increased IGF1 levels, IGF1 did not increase IGFBP5 levels in fibroblasts. The hearts of Otsuka Long-Evans Tokushima Fatty rats and the cardiac fibroblasts of streptozotocin-induced diabetic rats showed increased IGFBP5 expression. These results suggest that IGFBP5 mediates high glucose-induced profibrotic effects in cardiac fibroblasts.

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Section: Discussionsupporting

confidence: 78%

IGFBP5 mediates high glucose-induced cardiac fibroblast activation

Song¹,

Kim²,

Kim³

et al. 2013

Journal of Molecular Endocrinology

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“…Glucose (25 mmol/L) has also been shown to stimulate the phosphorylation of ERK1/2 in cardiac fibroblasts [12] . There were rare reports about the effect of glucose on the phosphorylation of NF-κB in cardiac fibroblasts.…”

Section: Resultsmentioning

confidence: 99%

“…Modulation of fibrosis signals in response to glucose and angiotensin II Previous studies have demonstrated that high concentrations of glucose promote cardiac secretion of collagens by fibroblasts [12] . In this study, we found that the expression of fibronectin, collagen-3A and collagen-4A was markedly increased in cardiac fibroblasts in response to glucose or Ang II.…”

Section: Resultsmentioning

confidence: 99%

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Effects of linagliptin and liraglutide on glucose- and angiotensin II-induced collagen formation and cytoskeleton degradation in cardiac fibroblasts in vitro

et al. 2016

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Aim: Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors can not only lower blood glucose levels, but also alleviate cardiac remodeling after myocardial ischemia and hypertension. In the present study, we investigated the effects of a DPP-4 inhibitor (linagliptin) and a GLP-1 activator (liraglutide) on glucose-and angiotensin II (Ang II)-induced collagen formation and cytoskeleton reorganization in cardiac fibroblasts in vitro, and elucidated the related mechanisms. Methods: Cardiac fibroblasts were isolated from the hearts of 6-week-old C57BL/6 mice, and then exposed to different concentrations of glucose or Ang II for 24 h. The expression of fibrotic signals (fibronectin, collagen-1, -3 and -4), as well as ERK1/2 and NF-κB-p65 in the fibroblasts was examined using Western blotting assays. F-actin degradation was detected under inverted laser confocal microscope in fibroblasts stained with Rhodamine phalloidin. Results: Glucose (1-40 mmol/L) and Ang II (10-5 mol/L) dose-dependently increased the expression of fibronectin, collagens, phospho-ERK1/2 and phospho-NF-κB-p65 in cardiac fibroblasts. High concentrations of glucose (≥40 mmol/L) and Ang II (≥10 -6 mol/L) caused a significant degradation of F-actin (less assembly F-actin fibers and more disassembly fibers). ERK1/2 inhibitor U0126 (10 μmol/L) and NF-κB inhibitor JSH-23 (10 μmol/L) both markedly suppressed glucose-and angiotensin II-induced fibronectin and collagen expressions in cardiac fibroblasts. Furthermore, pretreatment with liraglutide (10-100 nmol/L) or linagliptin (3 and 30 nmol/L) significantly decreased glucose-and Ang II-induced expression of fibrotic signals, phospho-ERK1/2 and phospho-NF-κB-p65 in cardiac fibroblasts. Moreover, pretreatment with liraglutide (30 nmol/L) or liraglutide (100 nmol/L) markedly inhibited glucose-induced F-actin degradation, however, only liraglutide inhibited Ang II-induced F-actin degradation. Conclusion: Linagliptin and liraglutide inhibit glucose-and Ang II-induced collagen formation in cardiac fibroblasts via activation of the ERK/NF-κB/pathway. Linagliptin and liraglutide also markedly inhibit glucose-induced F-actin degradation in cardiac fibroblasts, but only liraglutide inhibits Ang II-induced F-actin degradation.

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“…Cardiac fibroblasts also take a part in the maintenance of myocardial function by producing the type I and type III collagens and by secreting growth factors (48), and a key source of components of the ECM that regulates the structure of the heart and hence mechanical, chemical, and electrical signals between cellular and noncellular components (54). Thus cardiac fibroblasts play an essential role in the fibrosis and remodeling by increased proliferation (4) and elevated collagen production (61) under the various pathophysiological conditions such as diabetic cardiomyopathy (41).…”

mentioning

confidence: 99%

Effects of methylglyoxal on human cardiac fibroblast: roles of transient receptor potential ankyrin 1 (TRPA1) channels

Oguri

Nakajima

Yamamoto

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Effects of methylglyoxal on human cardiac fibroblast: roles of transient receptor potential ankyrin 1 (TRPA1) channels. Am J Physiol Heart Circ Physiol 307: H1339 -H1352, 2014. First published August 29, 2014; doi:10.1152/ajpheart.01021.2013.-Cardiac fibroblasts contribute to the pathogenesis of cardiac remodeling. Methylglyoxal (MG) is an endogenous carbonyl compound produced under hyperglycemic conditions, which may play a role in the development of pathophysiological conditions including diabetic cardiomyopathy. However, the mechanism by which this occurs and the molecular targets of MG are unclear. We investigated the effects of MG on Ca 2ϩ signals, its underlying mechanism, and cell cycle progression/cell differentiation in human cardiac fibroblasts. The conventional and quantitative real-time RT-PCR, Western blot, immunocytochemical analysis, and intracellular Ca 2ϩ concentration [Ca 2ϩ ]i measurement were applied. Cell cycle progression was assessed using the fluorescence activated cell sorting. MG induced Ca 2ϩ entry concentration dependently. Ruthenium red (RR), a general cation channel blocker, and HC030031, a selective transient receptor potential ankyrin 1 (TRPA1) antagonist, inhibited MG-induced Ca 2ϩ entry. Treatment with aminoguanidine, a MG scavenger, also inhibited it. Allyl isothiocyanate, a selective TRPA1 agonist, increased Ca 2ϩ entry. The use of small interfering RNA to knock down TRPA1 reduced the MGinduced Ca 2ϩ entry as well as TRPA1 mRNA expression. The quantitative real-time RT-PCR analysis showed the prominent existence of TRPA1 mRNA. Expression of TRPA1 protein was confirmed by Western blotting and immunocytochemical analyses. MG promoted cell cycle progression from G0/G1 to S/G2/M, which was suppressed by HC030031 or RR. MG also enhanced ␣-smooth muscle actin expression. The present results suggest that methylglyoxal activates TRPA1 and promotes cell cycle progression and differentiation in human cardiac fibroblasts. MG might participate the development of pathophysiological conditions including diabetic cardiomyopathy via activation of TRPA1.human cardiac fibroblast; transient receptor potential ankyrin 1 channels; methylglyoxal CARDIAC FIBROBLASTS ARE THE predominant secretary cell types located within the extracellular matrix (ECM) (18), which account for 60ϳ70% of the cells in human hearts and play a key role in regulating normal myocardial function and in the adverse myocardial remodeling that occurs with hypertension, heart failure, and myocardial infarction (12, 71). Many of the functional effects of cardiac fibroblasts are mediated through differentiation of cardiac fibroblasts to myofibroblasts phenotype that expresses contractile proteins such as ␣-smooth muscle actin (␣-SMA), and they consequently exhibit increased migratory and proliferative properties. Cardiac fibroblasts also take a part in the maintenance of myocardial function by producing the type I and type III collagens and by secreting growth factors (48), and a key source of components of the ECM that regulat...

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High glucose promotes the production of collagen types I and III by cardiac fibroblasts through a pathway dependent on extracellular-signal-regulated kinase 1/2

Cited by 64 publications

References 25 publications

IGFBP5 mediates high glucose-induced cardiac fibroblast activation

IGFBP5 mediates high glucose-induced cardiac fibroblast activation

Effects of linagliptin and liraglutide on glucose- and angiotensin II-induced collagen formation and cytoskeleton degradation in cardiac fibroblasts in vitro

Effects of methylglyoxal on human cardiac fibroblast: roles of transient receptor potential ankyrin 1 (TRPA1) channels

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