ERK1/2 mediates the lipopolysaccharide-induced upregulation of FGF-2, uPA, MMP-2, MMP-9 and cellular migration in cardiac fibroblasts

Chen, Liang-Chi; Shibu, Marthandam Asokan; Liu, Chung‐Jung; Han, Chien-Kuo; Ju, Da‐Tong; Chen, Pei-Yu; Viswanadha, Vijaya Padma; Lai, Chao-Hung; Kuo, Wei‐Wen; Huang, Chih‐Yang

doi:10.1016/j.cbi.2019.04.010

Cited by 26 publications

(16 citation statements)

References 57 publications

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“…Since the hypertrophic potential of FGF2 is effectively counteracted upon gene inactivation of Ephx2 , the cardiac remodeling role of FGF2 is attributed to the function of Ephx2, and subsequent activation of ERK1/2, but not AKT or p38 ( Zhang et al, 2014 ). A similar interaction between FGF2 and ERK1/2 in cardiac fibroblasts plays a role in the development of lipopolysaccharide (LPS)-triggered cardiac adverse events, leading to fibrosis and heart failure ( Chen et al, 2019 ). Along with an elevated number of cardiac mast cells in both ventricles under hypertrophic conditions, overexpression of Fgf2 may denote its pro-fibrotic role in the progress of myocardial fibrosis ( Kotov et al, 2020 ).…”

Section: Roles Of Fgf In Cardiac Pathophysiology and Repairmentioning

confidence: 99%

The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair

Khosravi

Ahmadvand

Bellusci

et al. 2021

Front. Cell Dev. Biol.

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The current focus on cardiovascular research reflects society’s concerns regarding the alarming incidence of cardiac-related diseases and mortality in the industrialized world and, notably, an urgent need to combat them by more efficient therapies. To pursue these therapeutic approaches, a comprehensive understanding of the mechanism of action for multifunctional fibroblast growth factor (FGF) signaling in the biology of the heart is a matter of high importance. The roles of FGFs in heart development range from outflow tract formation to the proliferation of cardiomyocytes and the formation of heart chambers. In the context of cardiac regeneration, FGFs 1, 2, 9, 16, 19, and 21 mediate adaptive responses including restoration of cardiac contracting rate after myocardial infarction and reduction of myocardial infarct size. However, cardiac complications in human diseases are correlated with pathogenic effects of FGF ligands and/or FGF signaling impairment. FGFs 2 and 23 are involved in maladaptive responses such as cardiac hypertrophic, fibrotic responses and heart failure. Among FGFs with known causative (FGFs 2, 21, and 23) or protective (FGFs 2, 15/19, 16, and 21) roles in cardiac diseases, FGFs 15/19, 21, and 23 display diagnostic potential. The effective role of FGFs on the induction of progenitor stem cells to cardiac cells during development has been employed to boost the limited capacity of postnatal cardiac repair. To renew or replenish damaged cardiomyocytes, FGFs 1, 2, 10, and 16 were tested in (induced-) pluripotent stem cell-based approaches and for stimulation of cell cycle re-entry in adult cardiomyocytes. This review will shed light on the wide range of beneficiary and detrimental actions mediated by FGF ligands and their receptors in the heart, which may open new therapeutic avenues for ameliorating cardiac complications.

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Section: Roles Of Fgf In Cardiac Pathophysiology and Repairmentioning

confidence: 99%

The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair

Khosravi

Ahmadvand

Bellusci

et al. 2021

Front. Cell Dev. Biol.

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“…To further verify the role of activated ERK1/2 in HCC cells, the MAPK/ERK1/2 inhibitor PD98059, which could inhibit phosphorylation of ERK1/2, was used ( 27 ). We treated QGY-7703 cells with GCDA (100 μM) or GCDA (100 μM) + PD98059 (10 μM) for 24, 48, and 72 h. Then, CCK8 was done to test the viability of QGY-7703 cells.…”

Section: Resultsmentioning

confidence: 99%

Suppressing ERK Pathway Impairs Glycochenodeoxycholate-Mediated Survival and Drug-Resistance in Hepatocellular Carcinoma Cells

Zhou

Wang

et al. 2021

Front. Oncol.

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Glycochenodeoxycholate (GCDA), a toxic component in bile salts, is involved in carcinogenesis of gastrointestinal tumors. The objective of this research was to study the function of ERK1/2 in the GCDA-mediated survival and drug-resistance in hepatocellular carcinoma cells (HCCs). Firstly, extracellular signal-regulated kinase 1/2 (ERK1/2) was detected extensively expressed in liver cancer cells, and silencing ERK1/2 by RNA interference could suppress GCDA-stimulated survival and promote apoptosis. Furthermore, phosphorylation of endogenous ERK1/2 could be potently stimulated by GCDA in combination with enhanced chemoresistance in QGY-7703 hepatocellular carcinoma cells. The GCDA-mediated proliferation and chemoresistance could be impaired by PD98059, which acted as an inhibitor to block the phosphorylation of ERK1/2. Mechanistically, PD98059 was able to potently suppress GCDA-stimulated nuclear aggregation of ERK1/2 and p-ERK1/2, upregulate pro-survival protein Mcl-1 and downregulate pro-apoptotic protein Bim. The results of this study indicated that disruption of ERK1/2 by blocking phosphorylation or nuclear translocation may put forward new methods for solving the problem of GCDA-related proliferation and drug-resistance in liver cancer treatment.

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“…To further verify the role of activated ERK1/2 in HCC cells, the MAPK/ERK1/2 inhibitor PD98059, which could inhibit phosphorylation of ERK1/2, was used (23). We treated QGY-7703 cells with GCDA (100µM) or GCDA (100µM) + PD98059 (10µM) for 24h, 48h and 72h.…”

Section: Resultsmentioning

confidence: 99%

Suppressing ERK Pathway Impairs Glycochenodeoxycholate-Mediated Survival and Drug-Resistance in Hepatocellular Carcinoma Cells

Zhou

Wang

et al. 2021

Preprint

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Background This research aims to examine the mechanism of glycochenodeoxycholate (GCDA)-mediated survival and drug-resistance in hepatocellular carcinoma cells (HCC). Extracellular signal-regulated kinase 1/2 (ERK1/2) were extensively expressed in liver cancer cells.Methods GCDA-induced survival of human liver carcinoma cells and chemoresistance was determined by CCK8 and flow cytometry, respectively. Functional of ERK1/2 and interaction of Bcl-2 family members was determined in western blot and immunofluorescence.Results Silencing ERK1/2 by RNA interference suppressed GCDA-stimulated survival and promoted apoptosis. Furthermore, phosphorylation of endogenous ERK1/2 could be potently stimulated by GCDA in combination with enhanced chemoresistance in QGY-7703 hepatocellular carcinoma cells. And such GCDA-mediated proliferation and chemoresistance could be impaired by PD98059, who acts as an inhibitor to block phosphorylation of ERK1/2. Mechanistically, PD98059 was able to potently suppress GCDA-stimulated nuclear aggregation of ERK1/2 and p-ERK1/2, up-regulation of pro-survival protein Mcl-1 and decrease of pro-apoptotic protein Bim.Conclusions Our work verified the function of ERK1/2 in GCDA-induced chemoresistance in hepatocellular carcinoma cells. Disruption of ERK1/2 by blocking phosphorylation or nuclear translocation may put forward new methods for treating of GCDA-related proliferation and drug-resistance in liver cancer.

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ERK1/2 mediates the lipopolysaccharide-induced upregulation of FGF-2, uPA, MMP-2, MMP-9 and cellular migration in cardiac fibroblasts

Cited by 26 publications

References 57 publications

The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair

The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair

Suppressing ERK Pathway Impairs Glycochenodeoxycholate-Mediated Survival and Drug-Resistance in Hepatocellular Carcinoma Cells

Suppressing ERK Pathway Impairs Glycochenodeoxycholate-Mediated Survival and Drug-Resistance in Hepatocellular Carcinoma Cells

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