Mechanism of TNF-α-induced migration and hepatocyte growth factor production in human mesenchymal stem cells

2010 ◽  
Vol 111 (2) ◽  
pp. 469-475 ◽  
Author(s):  
Aibin Zhang ◽  
Yan Wang ◽  
Zhou Ye ◽  
Haiyang Xie ◽  
Lin Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Human Mesenchymal Stem Cells ◽  
Factor Production ◽  
Tnf Α ◽  
Growth Factor Production ◽  
Hepatocyte Growth

Human mesenchymal stem cells stimulated by TNF-α, LPS, or hypoxia produce growth factors by an NFκB- but not JNK-dependent mechanism

2008 ◽  
Vol 294 (3) ◽  
pp. C675-C682 ◽  
Author(s):  
Paul R. Crisostomo ◽  
Yue Wang ◽  
Troy A. Markel ◽  
Meijing Wang ◽  
Tim Lahm ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Adult Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Human Mscs ◽  
Factor Production ◽  
Tnf Α ◽  
Growth Factor Production

Understanding the mechanisms by which adult stem cells produce growth factors may represent an important way to optimize their beneficial paracrine and autocrine effects. Components of the wound milieu may stimulate growth factor production to promote stem cell-mediated repair. We hypothesized that tumor necrosis factor-α (TNF-α), endotoxin (LPS), or hypoxia may activate human mesenchymal stem cells (MSCs) to increase release of vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), insulin-like growth factor 1 (IGF-1), or hepatocyte growth factor (HGF) and that nuclear factor-κB (NFκB), c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) mediates growth factor production from human MSCs. To study this, human MSCs were harvested, passaged, divided into four groups (100,000 cells, triplicates) and treated as follows: 1) with vehicle; 2) with stimulant alone [24 h LPS (200 ng/ml), 24 h TNF-α (50 ng/ml), or 24 h hypoxia (1% O2)]; 3) with inhibitor alone [NFκB (PDTC, 1 mM), JNK (TI-JIP, 10 μM), or ERK (ERK Inhibitor II, 25 μM)]; and 4) with stimulant and the various inhibitors. After 24 h incubation, MSC activation was determined by measuring supernatants for VEGF, FGF2, IGF-1, or HGF (ELISA). TNF-α, LPS, and hypoxia significantly increased human MSC VEGF, FGF2, HGF, and IGF-1 production versus controls. Stem cells exposed to injury demonstrated increased activation of NFκB, ERK, and JNK. VEGF, FGF2, and HGF expression was significantly reduced by NFκB inhibition (50% decrease) but not ERK or JNK inhibition. Moreover, ERK, JNK, and NFκB inhibitor alone did not activate MSC VEGF expression over controls. Various stressors activate human MSCs to increase VEGF, FGF2, HGF, and IGF-1 expression, which depends on an NFkB mechanism.

scholarly journals Hepatocyte Growth Factor and p38 Promote Osteogenic Differentiation of Human Mesenchymal Stem Cells

2014 ◽  
Vol 28 (5) ◽  
pp. 722-730 ◽  
Author(s):  
Kristina K. Aenlle ◽  
Kevin M. Curtis ◽  
Bernard A. Roos ◽  
Guy A. Howard
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Osteogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Transcriptional Level ◽  
Paracrine Factor ◽  
Osteogenic Markers ◽  
Hepatocyte Growth

Abstract Hepatocyte growth factor (HGF) is a paracrine factor involved in organogenesis, tissue repair, and wound healing. We report here that HGF promotes osteogenic differentiation through the transcription of key osteogenic markers, including osteocalcin, osterix, and osteoprotegerin in human mesenchymal stem cells and is a necessary component for the establishment of osteoblast mineralization. Blocking endogenous HGF using PHA665752, a c-Met inhibitor (the HGF receptor), or an HGF-neutralizing antibody attenuates mineralization, and PHA665752 markedly reduced alkaline phosphatase activity. Moreover, we report that HGF promotion of osteogenic differentiation involves the rapid phosphorylation of p38 and differential regulation of its isoforms, p38α and p38β. Western blot analysis revealed a significantly increased level of p38α and p38β protein, and reverse transcription quantitative PCR revealed that HGF increased the transcriptional level of both p38α and p38β. Using small interfering RNA to reduce the transcription of p38α and p38β, we saw differential roles for p38α and p38β on the HGF-induced expression of key osteogenic markers. In summary, our data demonstrate the importance of p38 signaling in HGF regulation of osteogenic differentiation.

T1773 Adenosine Inhibits Hepatocyte Growth Factor Induced Chemotaxis in Mesenchymal Stem Cells

2008 ◽  
Vol 134 (4) ◽  
pp. A-819
Author(s):  
Mehdi Mohamadnejad ◽  
Muhammad A. Sohail ◽  
Eugene S. Swenson ◽  
Wajahat Z. Mehal
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Hepatocyte Growth
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