ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential

Cárcamo-Orive, Iván; Tejados, Naiara; Delgado, Jesús; Gaztelumendi, Ainhoa; Otaegui, David; Lang, V. S.; Trigueros, César

doi:10.1016/j.yexcr.2008.01.020

Cited by 44 publications

(39 citation statements)

References 41 publications

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“…43) In agreement with the recent report, our data indicate that ERK2 play a key role in hepatocyte proliferation. [42][43][44][45] Moreover, EGF induction of ERK2 phosphorylation in hepatocytes was almost completely blocked by specific inhibitors of signal transducers, such as the EGF receptor tyrosine kinase inhibitor AG1478 and the MEK inhibitor PD98059, but not by LY294002 (PI3 kinase inhibitor) or rapamycin (mTOR inhibitor) (Fig. 2).…”

Section: Discussionmentioning

confidence: 92%

Activation of Extracellular-Signal Regulated Kinase by Epidermal Growth Factor Is Potentiated by cAMP-Elevating Agents in Primary Cultures of Adult Rat Hepatocytes

Moteki

Kimura

Ogihara

2011

Biological & Pharmaceutical Bulletin

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Epidermal growth factor (EGF) is well recognized as a potent mitogen, and appears to trigger liver regeneration after partial hepatectomy or after acute liver cell necrosis caused by chemicals in vivo. [1][2][3][4] The response of adult rat hepatocytes to EGF has also been extensively investigated with respect to DNA synthesis and proliferation in vitro. EGF is now known to be a potent hepatocyte mitogen and induces multiple biological activities in a wide variety of cell types. [5][6][7][8] More recently, we reported that EGF rapidly stimulates hepatocyte DNA synthesis and proliferation during short-term (e.g., 4 h) culture.9) In addition, the hepatocyte DNA synthesis and proliferation induced by EGF was inhibited depending on the initial plating density. Furthermore, we found that EGF-induced hepatocyte DNA synthesis and proliferation were potentiated by b 2 -adrenergic agonists. 9)The signal transduction pathways activated in response to EGF in hepatocytes and other cell types are now more clearly understood. [10][11][12] Using specific inhibitors of signal transducers, we pharmacologically demonstrated that EGF-receptor tyrosine kinase and ribosomal p70 S6 kinase activities, but not phosphoinositide 3-kinase (PI3K), are essential for EGFinduced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes. 9) PI3K is considered to be involved in hepatocyte growth factor (HGF) signal transduction. 13)In addition, extracellular-signal regulated kinase (ERK)1/2, also known as mitogen-activated protein kinase (p42/44 MAPK), is now known to be activated in response to a large number of mitogenic stimuli, and this enzyme is a key participant in the response to various growth factors and cytokines.14,15) In order to better understand the EGF-mediated signaling pathway, we investigated whether activation of the ERK isoforms, ERK1 and ERK2, is involved in EGFinduced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes.Catecholamines (e.g., norepinephrine and its analogs) have been shown to be involved in the regulation of liver function (e.g., lipid metabolism, carbohydrate metabolism and cell growth). There are several types of catecholamine receptors, b 1 -and b 2 -receptors, that stimulate adenylate cyclase (AC), while a 2 -receptor inhibits its phosphorylation. 5,16) a 1 -Receptor is involved in phospholipase C activation and subsequent increases in inositolphosphate turnover and diacylglycerol production.17,18) However, some investigators have reported that a 1 -and b-adrenergic responses are involved in adrenergic regulation of carbohydrate metabolism in the liver of normal adult rats and in cultured hepatocytes. 19,20) There are few studies regarding the adrenergic regulation of ERK1/2 phosphorylation induced by growth factors in liver cells. Therefore, in the present study, we examined whether a 1 -, a 2 -and b 2 -adrenergic agonists can modulate EGF-induced ERK1/2 isoform activities. The physiological significance of crosstalk between the EGF pathway and a 1 -, a 2 -and...

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Section: Discussionmentioning

confidence: 92%

Activation of Extracellular-Signal Regulated Kinase by Epidermal Growth Factor Is Potentiated by cAMP-Elevating Agents in Primary Cultures of Adult Rat Hepatocytes

Moteki

Kimura

Ogihara

2011

Biological & Pharmaceutical Bulletin

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“…Human CD34 þ cells RNAi was performed as described before. 37 The H1-shRNA expression cassette was excised from pSUPER vector and cloned in the lentiviral pLVTHM plasmid using EcoRI-ClaI sites. Viral particles were produced in human embryonic kidney 293T cells seeded in high-glucose DMEM containing 10% FBS.…”

Section: Measurement Of Extracellular Omentioning

confidence: 99%

p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation

et al. 2010

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Transient reactive oxygen species (ROS) production is currently proving to be an important mechanism in the regulation of intracellular signalling, but reports showing the involvement of ROS in important biological processes, such as cell differentiation, are scarce. In this study, we show for the first time that ROS production is required for megakaryocytic differentiation in K562 and HEL cell lines and also in human CD34 þ cells. ROS production is transiently activated during megakaryocytic differentiation, and such production is abolished by the addition of different antioxidants (such as N-acetyl cysteine, trolox, quercetin) or the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium. The inhibition of ROS formation hinders differentiation. RNA interference experiments have shown that a p22 phoxdependent NADPH oxidase activity is responsible for ROS production. In addition, the activation of ERK, AKT and JAK2 is required for differentiation, but the activation of phosphatidylinositol 3-kinase and c-Jun N-terminal kinase seems to be less important. When ROS production is prevented, the activation of these signalling pathways is partly inhibited. Taken together, these results show that NADPH oxidase ROS production is essential for complete activation of the main signalling pathways involved in megakaryocytopoiesis to occur. We suggest that this might also be important for in vivo megakaryocytopoiesis.

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“…33 For example, bFGF has been shown to promote proliferation but prevent osteogenic 34 or adipogenic 35 pluripotency through distinct pathways. The effect of bFGF on hMSC proliferation was mediated via Erk2 but not Erk1 mitogen-activated kinase.…”

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confidence: 99%

“…The effect of bFGF on hMSC proliferation was mediated via Erk2 but not Erk1 mitogen-activated kinase. 35 On the other hand, reduced myogenic differentiation by bFGF was attributed to decreased TGF-b2 expression, 36 but the mechanism remains elusive. It will be interesting to determine how bFGF prevents expression of genes that induce differentiation of HFCs to the myogenic lineage.…”

mentioning

confidence: 99%

Derivation of Functional Smooth Muscle Cells from Multipotent Human Hair Follicle Mesenchymal Stem Cells

Liu

Peng

Gopinath

et al. 2010

Tissue Engineering Part A

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We investigated the potential of human hair follicle cells for multilineage differentiation and as a source of functional smooth muscle cells (SMCs). We report that human hair follicle stem cells (HFCs) isolated from individual follicles expressed surface markers that are characteristic of mesenchymal stem cells such as CD44, CD49b, CD73, CD90, and CD105 but lacked hematopoietic markers CD45 and CD34. In addition, HFCs differentiated toward adipocytes, chondrocytes, osteoblasts, or SMCs in the appropriate induction medium. Treatment with basic fibroblast growth factor increased proliferation and prevented myogenic differentiation, suggesting that basic fibroblast growth factor can be used to expand the population of undifferentiated HFCs to the large numbers needed for therapeutic applications. SMCs were isolated from HFCs using tissue-specific promoters and flow cytometry sorting. Cylindrical vascular constructs engineered with HF-SMCs showed remarkable contractility in response to receptor and nonreceptor agonists such KCl, endothelin-1, and the thromboxane mimetic, U46619, as well as superior mechanical properties compared to their counterparts with human vascular SMCs. Our results suggest that HF is a rich source of mesenchymal stem cells with great potential for myogenic differentiation providing functional SMCs for tissue regeneration and cell therapies.

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ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential

Cited by 44 publications

References 41 publications

Activation of Extracellular-Signal Regulated Kinase by Epidermal Growth Factor Is Potentiated by cAMP-Elevating Agents in Primary Cultures of Adult Rat Hepatocytes

Activation of Extracellular-Signal Regulated Kinase by Epidermal Growth Factor Is Potentiated by cAMP-Elevating Agents in Primary Cultures of Adult Rat Hepatocytes

p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation

Derivation of Functional Smooth Muscle Cells from Multipotent Human Hair Follicle Mesenchymal Stem Cells

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