Induction by staurosporine of hepatocyte growth factor production in human skin fibroblasts independent of protein kinase inhibition

Yagi, Yasuyuki; Sotani, Tomohiro; Nagao, T; Horio, Tomoyo; Yamamoto, Ichiro; Gohda, Eiichi

doi:10.1016/s0006-2952(03)00547-1

Cited by 15 publications

(12 citation statements)

References 54 publications

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“…Protein in extracts was determined by a modification of the method of Lowry et al [41]. Equivalent protein aliquots were separated by 10% SDS-polyacrylamide gel electrophoresis (PAGE) and transfered electrophoretically to Immobilon-P membranes (Millipore, Billerica, MA, USA) as reported previously [42]. Blots were probed with various antibodies, incubated with horseradish peroxidase-conjugated donkey anti-rabbit immunoglobulins (GE Healthcare Bio-Sciences Corp., Piscataway, NJ, USA) and detected with ECL Plus Western blotting detection reagents (GE Healthcare Bio-Sciences Corp.).…”

Section: Western Blot Analysismentioning

confidence: 99%

Induction of hepatocyte growth factor production in human dermal fibroblasts and their proliferation by the extract of bitter melon pulp

et al. 2009

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Hepatocyte growth factor (HGF) is useful as a potential therapeutic agent for hepatic and renal fibrosis and cardiovascular diseases through inducing proliferation of epithelial and endothelial cells. HGF inducers may also be useful as therapeutic agents for these diseases. However, there have been no reports on induction of HGF production by plant extracts or juices. An extract of bitter melon (Momordica charantia L.) pulp markedly induced HGF production. There was a time lag of 72 h before induction of HGF production after the extract addition. Its stimulatory effect was accompanied by upregulation of HGF gene expression. Increases in mitogen-activated protein kinases (MAPKs) were observed from 72 h after the extract addition. Inhibitors of MAPKs suppressed the extract-induced HGF production. The extract also stimulated cell proliferation.Both activities for induction of HGF production and cell proliferation were eluted together in a single peak with 14 000 Da on gel filtration. The results indicate that bitter melon pulp extract induced HGF production and cell proliferation of human dermal fibroblasts and suggest that activation of MAPKs is involved in the HGF induction. Our findings suggest potential usefulness of the extract for tissue regeneration and provide an insight into the molecular mechanism underlying the wound-healing property of bitter melon.

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Section: Western Blot Analysismentioning

confidence: 99%

Induction of hepatocyte growth factor production in human dermal fibroblasts and their proliferation by the extract of bitter melon pulp

et al. 2009

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“…Another PKC inhibitor, staurosporine, caused an increase in basal p42/p44 MAPK activation. This could be due to the fact that staurosporine has been shown to increase hepatocyte growth factor production in a variety of cell types (Yagi, et al, 2003) and prostaglandin E2 production (Yamaki, et al, 2000). It is not known what effects these compounds have on conjunctival goblet cell secretion or p42/p44 MAPK activity.…”

Section: Discussionmentioning

confidence: 99%

Effect of protein kinase C and Ca2+ on p42/p44 MAPK, Pyk2, and Src activation in rat conjunctival goblet cells

Hodges

Horikawa

Ríos

et al. 2007

Experimental Eye Research

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Conjunctival goblet cells synthesize and secrete mucins onto the ocular surface to lubricate it and protect it from bacterial infections. Mucin secretion is under neural control, and cholinergic agonists released from parasympathetic nerves are major stimuli of this secretion. The signal transduction pathways these agonists use to stimulate secretion involve activating protein kinase C (PKC) and increasing intracellular [Ca 2+ ] to activate the non-receptor kinases Pyk2 and p60Src (Src) to transactivate the EGF receptor. Transactivation of the EGF receptor activates a kinase cascade culminating in the activation of p42/p44 MAPK (MAPK) and ultimately that leads to secretion of high molecular weight glycocongujates (HMWGC), including mucins. To further examine the roles of PKC and Ca 2+ in the activation of MAPK, Pyk2, and Src in mucin secretion, rat conjunctival pieces and cultured goblet cells were incubated with the PKC activator phorbol myristate acid (PMA), the cholinergic agonist carbachol, or the calcium ionophore, ionomycin for varying times. Conjunctival pieces were preincubated with PKC inhibitors 10 mins prior to addition of carbachol (10 −4 M) for 10 min. The amount of phosphorylated (activated) MAPK, Pyk2 and Src was determined by western blotting techniques using antibodies specific to the phosphorylated forms of each kinase. PMA significantly increased the activation of MAPK, Pyk2, and Src in a time and concentrationdependent manner. PMA-stimulated MAPK activity was completely inhibited by the EGF receptor inhibitor AG1478 (10 −7 M). Carbachol-stimulated MAPK activity was inhibited by three PKC inhibitors, calphostin C, chelethyrine, and staurosporine. Ionomycin (10 −6 M)-stimulated MAPK activity was inhibited 66% by AG1478 (10 −7 M). Ionomycin also significantly increased Pyk2 and Src in time dependent manner. PKC and ionomycin also activated p42/p44 MAPL, Pyk2, and Src in cultured conjunctival goblet cells. We conclude that PKC and intracellular Ca 2+ activate Pyk2 and Src and phosphorylated the EGF receptor leading to stimulation of MAPK in conjunctival goblet cells. Keywords goblet cells; signal transduction; MAPK; mucin secretionGoblet cells of the conjunctiva are responsible for synthesis, storage, and secretion of mucins, which make up the mucous layer of the tear film (Dartt, 2004, Gipson andArgueso, 2003). Mucins serve to lubricate the ocular surface, protect from bacterial infections and provide for a smooth refractive surface. These cells are highly specialized epithelial cells that are * author to whom correspondence should be addressed: 20 Staniford Street, Boston, MA 02114. Tel: 617-912-7424; FAX: 617-912-0104; email: robin.hodges@schepens.harvard.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form...

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“…Protein in extracts was determined by a modification of the method of Lowry et al 40,41) Western blotting was performed as described previously. 32) Briefly, protein aliquots (each 10 mg) were separated by 10% SDS-PAGE and transferred electrophoretically to Immobilon-P transfer membranes (Millipore, Billerica, MA, U.S.A.). The membranes were then probed with anti-phospho-p44/42 MAPK antibody or antip44 MAPK antibody and then incubated with horseradish peroxidase-conjugated donkey anti-rabbit IgG (Amersham Biosciences, Little Chalfont, England) and detected with ECL Plus Western blotting detection reagents (Amersham Biosciences, Little Chalfont, England).…”

Section: Determination Of Hgf Levels In Conditioned Mediamentioning

confidence: 99%

“…[21][22][23] Its production is also stimulated by interleukin-1, tumor necrosis factor-a, estrogen, ascorbic acid, okadaic acid, norepinephrine, staurosporine, a scatter factor-inducing factor, and various growth factors. [24][25][26][27][28][29][30][31][32] Conversely, HGF production is inhibited by transforming growth factor (TGF)-b, glucocorticoids, 1,25-dihydroxyvitamin D 3 , and retinoic acid. 21,22,[33][34][35][36] Prompted by the increase in the number of identified modulators for HGF production, we previously examined whether drugs used for the treatment of liver diseases modulate HGF production and HGF induction and reported that interferon (IFN)-g, -a, and -b, which are used for the treatment of tumors and chronic hepatitis C and hepatitis B, are potent inducers of HGF in human leukemia cells.…”

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confidence: 99%

Inhibition of Hepatocyte Growth Factor Production in Human Fibroblasts by Ursodeoxycholic Acid

Hiramatsu

Matsumoto

Miyazaki

et al. 2005

Biological & Pharmaceutical Bulletin

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Hepatocyte growth factor (HGF) stimulates the proliferation of hepatocytes and biliary epithelial cells and protects hepatocytes from apoptosis induced by various stimuli. In view of HGF induction by interferons, substances used for the treatment of chronic hepatitis C, this study was conducted to determine whether ursodeoxycholic acid (UDCA), which is widely used for the treatment of cholestatic liver diseases,

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Induction by staurosporine of hepatocyte growth factor production in human skin fibroblasts independent of protein kinase inhibition

Cited by 15 publications

References 54 publications

Induction of hepatocyte growth factor production in human dermal fibroblasts and their proliferation by the extract of bitter melon pulp

Induction of hepatocyte growth factor production in human dermal fibroblasts and their proliferation by the extract of bitter melon pulp

Effect of protein kinase C and Ca2+ on p42/p44 MAPK, Pyk2, and Src activation in rat conjunctival goblet cells

Inhibition of Hepatocyte Growth Factor Production in Human Fibroblasts by Ursodeoxycholic Acid

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