PDGF stimulation of Müller cell proliferation: Contributions of c-JNK and the PI3K/Akt pathway
Platelet-derived growth factor (PDGF) has a critical role in proliferative vitreoretinopathy (PVR) as a chemoattractant and mitogen for retinal pigment epithelial cells and retinal glial cells. Here, we investigated the potential effects of PDGF on the proliferation of Müller cells and the intracell...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2009-10, Vol.388 (1), p.167-171 |
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| creator | Moon, Sang Woong Chung, Eun Jee Jung, Sun-Ah Lee, Joon H. |
| description | Platelet-derived growth factor (PDGF) has a critical role in proliferative vitreoretinopathy (PVR) as a chemoattractant and mitogen for retinal pigment epithelial cells and retinal glial cells. Here, we investigated the potential effects of PDGF on the proliferation of Müller cells and the intracellular signaling pathway mediating these changes. PDGF induced Müller cell proliferation and increased phosphorylation of the PDGF receptor (PDGFR), as shown by an MTT assay and immunoprecipitation analyses. Both effects were blocked by JNJ, a PDGFR-selective tyrosine kinase inhibitor. PDGF also stimulated phosphorylation of c-JNK and Akt. PDGF-induced Müller cell proliferation was significantly reduced by pre-treatment with SP600125 and LY294002, inhibitors of c-JNK and Akt phosphorylation, respectively. Our findings collectively indicate that PDGF-stimulated Müller cell proliferation occurs via activation of the c-JNK and PI3K/Akt signaling pathways. These data provide useful information in establishing the role of Müller cells in the development of proliferative vitreoretinopathy. |
| doi_str_mv | 10.1016/j.bbrc.2009.07.144 |
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Here, we investigated the potential effects of PDGF on the proliferation of Müller cells and the intracellular signaling pathway mediating these changes. PDGF induced Müller cell proliferation and increased phosphorylation of the PDGF receptor (PDGFR), as shown by an MTT assay and immunoprecipitation analyses. Both effects were blocked by JNJ, a PDGFR-selective tyrosine kinase inhibitor. PDGF also stimulated phosphorylation of c-JNK and Akt. PDGF-induced Müller cell proliferation was significantly reduced by pre-treatment with SP600125 and LY294002, inhibitors of c-JNK and Akt phosphorylation, respectively. Our findings collectively indicate that PDGF-stimulated Müller cell proliferation occurs via activation of the c-JNK and PI3K/Akt signaling pathways. These data provide useful information in establishing the role of Müller cells in the development of proliferative vitreoretinopathy.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2009.07.144</identifier><identifier>PMID: 19653997</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Anthracenes - pharmacology ; Cell Proliferation ; Chromones - pharmacology ; Enzyme Inhibitors - pharmacology ; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors ; JNK Mitogen-Activated Protein Kinases - physiology ; Morpholines - pharmacology ; Müller cell ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Phosphatidylinositol 3-Kinases - physiology ; Platelet-derived growth factor ; Platelet-Derived Growth Factor - pharmacology ; Platelet-Derived Growth Factor - physiology ; Proliferative vitreoretinopathy ; Proto-Oncogene Proteins c-akt - antagonists & inhibitors ; Proto-Oncogene Proteins c-akt - physiology ; Rats ; Rats, Inbred BN ; Receptors, Platelet-Derived Growth Factor - agonists ; Receptors, Platelet-Derived Growth Factor - metabolism ; Retina - metabolism ; Retina - pathology ; Vitreoretinopathy, Proliferative - metabolism ; Vitreoretinopathy, Proliferative - pathology</subject><ispartof>Biochemical and biophysical research communications, 2009-10, Vol.388 (1), p.167-171</ispartof><rights>2009 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-4cad0eb2d167b3e8cca00f4780a635785fdb9e4768d5632333518a5669f80fa33</citedby><cites>FETCH-LOGICAL-c385t-4cad0eb2d167b3e8cca00f4780a635785fdb9e4768d5632333518a5669f80fa33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X09015198$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19653997$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moon, Sang Woong</creatorcontrib><creatorcontrib>Chung, Eun Jee</creatorcontrib><creatorcontrib>Jung, Sun-Ah</creatorcontrib><creatorcontrib>Lee, Joon H.</creatorcontrib><title>PDGF stimulation of Müller cell proliferation: Contributions of c-JNK and the PI3K/Akt pathway</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Platelet-derived growth factor (PDGF) has a critical role in proliferative vitreoretinopathy (PVR) as a chemoattractant and mitogen for retinal pigment epithelial cells and retinal glial cells. Here, we investigated the potential effects of PDGF on the proliferation of Müller cells and the intracellular signaling pathway mediating these changes. PDGF induced Müller cell proliferation and increased phosphorylation of the PDGF receptor (PDGFR), as shown by an MTT assay and immunoprecipitation analyses. Both effects were blocked by JNJ, a PDGFR-selective tyrosine kinase inhibitor. PDGF also stimulated phosphorylation of c-JNK and Akt. PDGF-induced Müller cell proliferation was significantly reduced by pre-treatment with SP600125 and LY294002, inhibitors of c-JNK and Akt phosphorylation, respectively. Our findings collectively indicate that PDGF-stimulated Müller cell proliferation occurs via activation of the c-JNK and PI3K/Akt signaling pathways. These data provide useful information in establishing the role of Müller cells in the development of proliferative vitreoretinopathy.</description><subject>Animals</subject><subject>Anthracenes - pharmacology</subject><subject>Cell Proliferation</subject><subject>Chromones - pharmacology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>JNK Mitogen-Activated Protein Kinases - physiology</subject><subject>Morpholines - pharmacology</subject><subject>Müller cell</subject><subject>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</subject><subject>Phosphatidylinositol 3-Kinases - physiology</subject><subject>Platelet-derived growth factor</subject><subject>Platelet-Derived Growth Factor - pharmacology</subject><subject>Platelet-Derived Growth Factor - physiology</subject><subject>Proliferative vitreoretinopathy</subject><subject>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-akt - physiology</subject><subject>Rats</subject><subject>Rats, Inbred BN</subject><subject>Receptors, Platelet-Derived Growth Factor - agonists</subject><subject>Receptors, Platelet-Derived Growth Factor - metabolism</subject><subject>Retina - metabolism</subject><subject>Retina - pathology</subject><subject>Vitreoretinopathy, Proliferative - metabolism</subject><subject>Vitreoretinopathy, Proliferative - pathology</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi0EotvCH-CAfOKWdGwn_kBcqoWW0gI9gMTNcpyJ6iWbbG0H1P_WG3-MhF2JG5xGo3neV6OHkBcMSgZMnm7Kpom-5ACmBFWyqnpEVgwMFJxB9ZisAEAW3LBvR-Q4pQ0AY5U0T8kRM7IWxqgVsTdvL85pymE79S6HcaBjRz_-euh7jNRj39NdHPvQYfxzfU3X45BjaKZlSwvsiw-frqgbWppvkd5ciqvTs--Z7ly-_enun5EnnesTPj_ME_L1_N2X9fvi-vPF5frsuvBC17movGsBG94yqRqB2nsH0FVKg5OiVrru2sZgpaRuaym4EKJm2tVSmk5D54Q4Ia_2vfO7dxOmbLchLf-7AccpWakkaM7_D3JQIKTmM8j3oI9jShE7u4th6-K9ZWAX_3ZjF_928W9B2dn_HHp5aJ-aLbZ_IwfhM_BmD-As40fAaJMPOHhsQ0SfbTuGf_X_BuxHlfU</recordid><startdate>20091009</startdate><enddate>20091009</enddate><creator>Moon, Sang Woong</creator><creator>Chung, Eun Jee</creator><creator>Jung, Sun-Ah</creator><creator>Lee, Joon H.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>20091009</creationdate><title>PDGF stimulation of Müller cell proliferation: Contributions of c-JNK and the PI3K/Akt pathway</title><author>Moon, Sang Woong ; Chung, Eun Jee ; Jung, Sun-Ah ; Lee, Joon H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-4cad0eb2d167b3e8cca00f4780a635785fdb9e4768d5632333518a5669f80fa33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Anthracenes - pharmacology</topic><topic>Cell Proliferation</topic><topic>Chromones - pharmacology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>JNK Mitogen-Activated Protein Kinases - physiology</topic><topic>Morpholines - pharmacology</topic><topic>Müller cell</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Phosphatidylinositol 3-Kinases - physiology</topic><topic>Platelet-derived growth factor</topic><topic>Platelet-Derived Growth Factor - pharmacology</topic><topic>Platelet-Derived Growth Factor - physiology</topic><topic>Proliferative vitreoretinopathy</topic><topic>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - physiology</topic><topic>Rats</topic><topic>Rats, Inbred BN</topic><topic>Receptors, Platelet-Derived Growth Factor - agonists</topic><topic>Receptors, Platelet-Derived Growth Factor - metabolism</topic><topic>Retina - metabolism</topic><topic>Retina - pathology</topic><topic>Vitreoretinopathy, Proliferative - metabolism</topic><topic>Vitreoretinopathy, Proliferative - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moon, Sang Woong</creatorcontrib><creatorcontrib>Chung, Eun Jee</creatorcontrib><creatorcontrib>Jung, Sun-Ah</creatorcontrib><creatorcontrib>Lee, Joon H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moon, Sang Woong</au><au>Chung, Eun Jee</au><au>Jung, Sun-Ah</au><au>Lee, Joon H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PDGF stimulation of Müller cell proliferation: Contributions of c-JNK and the PI3K/Akt pathway</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2009-10-09</date><risdate>2009</risdate><volume>388</volume><issue>1</issue><spage>167</spage><epage>171</epage><pages>167-171</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Platelet-derived growth factor (PDGF) has a critical role in proliferative vitreoretinopathy (PVR) as a chemoattractant and mitogen for retinal pigment epithelial cells and retinal glial cells. 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| subjects | Animals Anthracenes - pharmacology Cell Proliferation Chromones - pharmacology Enzyme Inhibitors - pharmacology JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors JNK Mitogen-Activated Protein Kinases - physiology Morpholines - pharmacology Müller cell Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - physiology Platelet-derived growth factor Platelet-Derived Growth Factor - pharmacology Platelet-Derived Growth Factor - physiology Proliferative vitreoretinopathy Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - physiology Rats Rats, Inbred BN Receptors, Platelet-Derived Growth Factor - agonists Receptors, Platelet-Derived Growth Factor - metabolism Retina - metabolism Retina - pathology Vitreoretinopathy, Proliferative - metabolism Vitreoretinopathy, Proliferative - pathology |
| title | PDGF stimulation of Müller cell proliferation: Contributions of c-JNK and the PI3K/Akt pathway |
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