Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway
Activated pancreatic stellate cells (PSCs) play major roles in promoting pancreatic fibrosis. We previously reported that angiotensin II (Ang II) enhances activated PSC proliferation through EGF receptor transactivation. In the present study, we elucidated a novel intracellular mechanism by which An...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2006-02, Vol.340 (3), p.742-750 |
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| creator | Hama, Kouji Ohnishi, Hirohide Aoki, Hiroyoshi Kita, Hiroto Yamamoto, Hironori Osawa, Hiroyuki Sato, Kiichi Tamada, Kiichi Mashima, Hirosato Yasuda, Hiroshi Sugano, Kentaro |
| description | Activated pancreatic stellate cells (PSCs) play major roles in promoting pancreatic fibrosis. We previously reported that angiotensin II (Ang II) enhances activated PSC proliferation through EGF receptor transactivation. In the present study, we elucidated a novel intracellular mechanism by which Ang II stimulates cellular proliferation. TGF-β
1 inhibits activated PSC proliferation via a Smad3 and Smad4-dependent pathway in an autocrine manner. We demonstrated that Ang II inhibited TGF-β
1-induced nuclear accumulation of Smad3 and Smad4. Furthermore, Ang II rapidly induced inhibitory Smad7 mRNA expression. Adenovirus-mediated Smad7 overexpression inhibited TGF-β
1-induced nuclear accumulation of Smad3 and Smad4, and potentiated activated PSC proliferation. PKC inhibitor Go6983 blocked the induction of Smad7 mRNA expression by Ang II. In addition, 12-
O-tetradecanoyl-phorbol 13-acetate, a PKC activator, increased Smad7 mRNA expression. These results suggest that Ang II enhances activated PSC proliferation by blocking autocrine TGF-β
1-mediated growth inhibition by inducing Smad7 expression via a PKC-dependent pathway. |
| doi_str_mv | 10.1016/j.bbrc.2005.12.069 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_osti_</sourceid><recordid>TN_cdi_osti_scitechconnect_20798802</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006291X05028202</els_id><sourcerecordid>19766295</sourcerecordid><originalsourceid>FETCH-LOGICAL-c479t-8096b4ca87c14c7b46b1731892c33e3be7a881dcc0664f734dfa4597785ffec83</originalsourceid><addsrcrecordid>eNp9kc-KFDEQxoMo7uzqC3iQgOCt20q6J3_AyzLoOrDgQQVvIZ2u3s44kx6T9Mq8gM9t2hnw5qmo5FdffclHyCsGNQMm3u3qrouu5gDrmvEahH5CVgw0VJxB-5SsAEBUXLPvV-Q6pR0AY63Qz8kVE40CUGxFft-GBz9lDMkHut3SY5wOpU00j7g0ez9gtNlPgU4DtS77R5uxp0cbXMRy4WjKuN-XQ-pKTbQ70S8H20vqQz-7v5N5jNP8MFK7KGYsm374YBPSTdHJ4y97ekGeDXaf8OWl3pBvHz983Xyq7j_fbTe395Vrpc6VAi261lklHWud7FrRMdkwpblrGmw6lFYp1jsHQrSDbNp-sO1aS6nWw4BONTfkzVl3Stmb5HxGN7opBHTZcJBaKeCFenumit2fM6ZsDj4tr7MBpzkZpqUQXK8LyM-gi1NKEQdzjP5g48kwMEtGZmeWjMySkWHclIzK0OuL-twdsP83cgmlAO_PAJafePQYF6MYHPY-Lj77yf9P_w8hwKRk</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>19766295</pqid></control><display><type>article</type><title>Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Hama, Kouji ; Ohnishi, Hirohide ; Aoki, Hiroyoshi ; Kita, Hiroto ; Yamamoto, Hironori ; Osawa, Hiroyuki ; Sato, Kiichi ; Tamada, Kiichi ; Mashima, Hirosato ; Yasuda, Hiroshi ; Sugano, Kentaro</creator><creatorcontrib>Hama, Kouji ; Ohnishi, Hirohide ; Aoki, Hiroyoshi ; Kita, Hiroto ; Yamamoto, Hironori ; Osawa, Hiroyuki ; Sato, Kiichi ; Tamada, Kiichi ; Mashima, Hirosato ; Yasuda, Hiroshi ; Sugano, Kentaro</creatorcontrib><description>Activated pancreatic stellate cells (PSCs) play major roles in promoting pancreatic fibrosis. We previously reported that angiotensin II (Ang II) enhances activated PSC proliferation through EGF receptor transactivation. In the present study, we elucidated a novel intracellular mechanism by which Ang II stimulates cellular proliferation. TGF-β
1 inhibits activated PSC proliferation via a Smad3 and Smad4-dependent pathway in an autocrine manner. We demonstrated that Ang II inhibited TGF-β
1-induced nuclear accumulation of Smad3 and Smad4. Furthermore, Ang II rapidly induced inhibitory Smad7 mRNA expression. Adenovirus-mediated Smad7 overexpression inhibited TGF-β
1-induced nuclear accumulation of Smad3 and Smad4, and potentiated activated PSC proliferation. PKC inhibitor Go6983 blocked the induction of Smad7 mRNA expression by Ang II. In addition, 12-
O-tetradecanoyl-phorbol 13-acetate, a PKC activator, increased Smad7 mRNA expression. These results suggest that Ang II enhances activated PSC proliferation by blocking autocrine TGF-β
1-mediated growth inhibition by inducing Smad7 expression via a PKC-dependent pathway.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2005.12.069</identifier><identifier>PMID: 16380081</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ACETATES ; Adenoviridae - metabolism ; ADENOVIRUS ; ANGIOTENSIN ; Angiotensin II ; Angiotensin II - metabolism ; Angiotensin II - physiology ; Animals ; Blotting, Western ; Carbazoles - pharmacology ; Cell Nucleus - metabolism ; CELL PROLIFERATION ; Cells, Cultured ; DNA - metabolism ; Dose-Response Relationship, Drug ; Enzyme Activation ; Enzyme Inhibitors - pharmacology ; FIBROSIS ; Fibrosis - pathology ; GROWTH ; Immunohistochemistry ; Indoles ; INHIBITION ; Maleimides ; NF-kappa B - metabolism ; NF-κB ; OXYGEN 12 ; PANCREAS ; Pancreas - cytology ; Pancreas - metabolism ; Pancreas - pathology ; Pancreatic stellate cell ; Proliferation ; Protein kinase C ; Protein Kinase C - metabolism ; Rats ; Receptor, Epidermal Growth Factor - metabolism ; RECEPTORS ; RNA, Messenger - metabolism ; Signal Transduction ; Smad ; Smad3 Protein - metabolism ; Smad4 Protein - metabolism ; Smad7 Protein - metabolism ; Tetradecanoylphorbol Acetate - pharmacology ; TGF-β ; Time Factors ; Transcriptional Activation ; Transforming Growth Factor beta - metabolism ; Transforming Growth Factor beta1</subject><ispartof>Biochemical and biophysical research communications, 2006-02, Vol.340 (3), p.742-750</ispartof><rights>2005 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-8096b4ca87c14c7b46b1731892c33e3be7a881dcc0664f734dfa4597785ffec83</citedby><cites>FETCH-LOGICAL-c479t-8096b4ca87c14c7b46b1731892c33e3be7a881dcc0664f734dfa4597785ffec83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2005.12.069$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16380081$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/20798802$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Hama, Kouji</creatorcontrib><creatorcontrib>Ohnishi, Hirohide</creatorcontrib><creatorcontrib>Aoki, Hiroyoshi</creatorcontrib><creatorcontrib>Kita, Hiroto</creatorcontrib><creatorcontrib>Yamamoto, Hironori</creatorcontrib><creatorcontrib>Osawa, Hiroyuki</creatorcontrib><creatorcontrib>Sato, Kiichi</creatorcontrib><creatorcontrib>Tamada, Kiichi</creatorcontrib><creatorcontrib>Mashima, Hirosato</creatorcontrib><creatorcontrib>Yasuda, Hiroshi</creatorcontrib><creatorcontrib>Sugano, Kentaro</creatorcontrib><title>Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Activated pancreatic stellate cells (PSCs) play major roles in promoting pancreatic fibrosis. We previously reported that angiotensin II (Ang II) enhances activated PSC proliferation through EGF receptor transactivation. In the present study, we elucidated a novel intracellular mechanism by which Ang II stimulates cellular proliferation. TGF-β
1 inhibits activated PSC proliferation via a Smad3 and Smad4-dependent pathway in an autocrine manner. We demonstrated that Ang II inhibited TGF-β
1-induced nuclear accumulation of Smad3 and Smad4. Furthermore, Ang II rapidly induced inhibitory Smad7 mRNA expression. Adenovirus-mediated Smad7 overexpression inhibited TGF-β
1-induced nuclear accumulation of Smad3 and Smad4, and potentiated activated PSC proliferation. PKC inhibitor Go6983 blocked the induction of Smad7 mRNA expression by Ang II. In addition, 12-
O-tetradecanoyl-phorbol 13-acetate, a PKC activator, increased Smad7 mRNA expression. These results suggest that Ang II enhances activated PSC proliferation by blocking autocrine TGF-β
1-mediated growth inhibition by inducing Smad7 expression via a PKC-dependent pathway.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ACETATES</subject><subject>Adenoviridae - metabolism</subject><subject>ADENOVIRUS</subject><subject>ANGIOTENSIN</subject><subject>Angiotensin II</subject><subject>Angiotensin II - metabolism</subject><subject>Angiotensin II - physiology</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Carbazoles - pharmacology</subject><subject>Cell Nucleus - metabolism</subject><subject>CELL PROLIFERATION</subject><subject>Cells, Cultured</subject><subject>DNA - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Activation</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>FIBROSIS</subject><subject>Fibrosis - pathology</subject><subject>GROWTH</subject><subject>Immunohistochemistry</subject><subject>Indoles</subject><subject>INHIBITION</subject><subject>Maleimides</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB</subject><subject>OXYGEN 12</subject><subject>PANCREAS</subject><subject>Pancreas - cytology</subject><subject>Pancreas - metabolism</subject><subject>Pancreas - pathology</subject><subject>Pancreatic stellate cell</subject><subject>Proliferation</subject><subject>Protein kinase C</subject><subject>Protein Kinase C - metabolism</subject><subject>Rats</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>RECEPTORS</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction</subject><subject>Smad</subject><subject>Smad3 Protein - metabolism</subject><subject>Smad4 Protein - metabolism</subject><subject>Smad7 Protein - metabolism</subject><subject>Tetradecanoylphorbol Acetate - pharmacology</subject><subject>TGF-β</subject><subject>Time Factors</subject><subject>Transcriptional Activation</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Transforming Growth Factor beta1</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc-KFDEQxoMo7uzqC3iQgOCt20q6J3_AyzLoOrDgQQVvIZ2u3s44kx6T9Mq8gM9t2hnw5qmo5FdffclHyCsGNQMm3u3qrouu5gDrmvEahH5CVgw0VJxB-5SsAEBUXLPvV-Q6pR0AY63Qz8kVE40CUGxFft-GBz9lDMkHut3SY5wOpU00j7g0ez9gtNlPgU4DtS77R5uxp0cbXMRy4WjKuN-XQ-pKTbQ70S8H20vqQz-7v5N5jNP8MFK7KGYsm374YBPSTdHJ4y97ekGeDXaf8OWl3pBvHz983Xyq7j_fbTe395Vrpc6VAi261lklHWud7FrRMdkwpblrGmw6lFYp1jsHQrSDbNp-sO1aS6nWw4BONTfkzVl3Stmb5HxGN7opBHTZcJBaKeCFenumit2fM6ZsDj4tr7MBpzkZpqUQXK8LyM-gi1NKEQdzjP5g48kwMEtGZmeWjMySkWHclIzK0OuL-twdsP83cgmlAO_PAJafePQYF6MYHPY-Lj77yf9P_w8hwKRk</recordid><startdate>20060217</startdate><enddate>20060217</enddate><creator>Hama, Kouji</creator><creator>Ohnishi, Hirohide</creator><creator>Aoki, Hiroyoshi</creator><creator>Kita, Hiroto</creator><creator>Yamamoto, Hironori</creator><creator>Osawa, Hiroyuki</creator><creator>Sato, Kiichi</creator><creator>Tamada, Kiichi</creator><creator>Mashima, Hirosato</creator><creator>Yasuda, Hiroshi</creator><creator>Sugano, Kentaro</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>7U9</scope><scope>H94</scope><scope>OTOTI</scope></search><sort><creationdate>20060217</creationdate><title>Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway</title><author>Hama, Kouji ; Ohnishi, Hirohide ; Aoki, Hiroyoshi ; Kita, Hiroto ; Yamamoto, Hironori ; Osawa, Hiroyuki ; Sato, Kiichi ; Tamada, Kiichi ; Mashima, Hirosato ; Yasuda, Hiroshi ; Sugano, Kentaro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-8096b4ca87c14c7b46b1731892c33e3be7a881dcc0664f734dfa4597785ffec83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ACETATES</topic><topic>Adenoviridae - metabolism</topic><topic>ADENOVIRUS</topic><topic>ANGIOTENSIN</topic><topic>Angiotensin II</topic><topic>Angiotensin II - metabolism</topic><topic>Angiotensin II - physiology</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Carbazoles - pharmacology</topic><topic>Cell Nucleus - metabolism</topic><topic>CELL PROLIFERATION</topic><topic>Cells, Cultured</topic><topic>DNA - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Activation</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>FIBROSIS</topic><topic>Fibrosis - pathology</topic><topic>GROWTH</topic><topic>Immunohistochemistry</topic><topic>Indoles</topic><topic>INHIBITION</topic><topic>Maleimides</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB</topic><topic>OXYGEN 12</topic><topic>PANCREAS</topic><topic>Pancreas - cytology</topic><topic>Pancreas - metabolism</topic><topic>Pancreas - pathology</topic><topic>Pancreatic stellate cell</topic><topic>Proliferation</topic><topic>Protein kinase C</topic><topic>Protein Kinase C - metabolism</topic><topic>Rats</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>RECEPTORS</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction</topic><topic>Smad</topic><topic>Smad3 Protein - metabolism</topic><topic>Smad4 Protein - metabolism</topic><topic>Smad7 Protein - metabolism</topic><topic>Tetradecanoylphorbol Acetate - pharmacology</topic><topic>TGF-β</topic><topic>Time Factors</topic><topic>Transcriptional Activation</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Transforming Growth Factor beta1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hama, Kouji</creatorcontrib><creatorcontrib>Ohnishi, Hirohide</creatorcontrib><creatorcontrib>Aoki, Hiroyoshi</creatorcontrib><creatorcontrib>Kita, Hiroto</creatorcontrib><creatorcontrib>Yamamoto, Hironori</creatorcontrib><creatorcontrib>Osawa, Hiroyuki</creatorcontrib><creatorcontrib>Sato, Kiichi</creatorcontrib><creatorcontrib>Tamada, Kiichi</creatorcontrib><creatorcontrib>Mashima, Hirosato</creatorcontrib><creatorcontrib>Yasuda, Hiroshi</creatorcontrib><creatorcontrib>Sugano, Kentaro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>OSTI.GOV</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hama, Kouji</au><au>Ohnishi, Hirohide</au><au>Aoki, Hiroyoshi</au><au>Kita, Hiroto</au><au>Yamamoto, Hironori</au><au>Osawa, Hiroyuki</au><au>Sato, Kiichi</au><au>Tamada, Kiichi</au><au>Mashima, Hirosato</au><au>Yasuda, Hiroshi</au><au>Sugano, Kentaro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2006-02-17</date><risdate>2006</risdate><volume>340</volume><issue>3</issue><spage>742</spage><epage>750</epage><pages>742-750</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Activated pancreatic stellate cells (PSCs) play major roles in promoting pancreatic fibrosis. We previously reported that angiotensin II (Ang II) enhances activated PSC proliferation through EGF receptor transactivation. In the present study, we elucidated a novel intracellular mechanism by which Ang II stimulates cellular proliferation. TGF-β
1 inhibits activated PSC proliferation via a Smad3 and Smad4-dependent pathway in an autocrine manner. We demonstrated that Ang II inhibited TGF-β
1-induced nuclear accumulation of Smad3 and Smad4. Furthermore, Ang II rapidly induced inhibitory Smad7 mRNA expression. Adenovirus-mediated Smad7 overexpression inhibited TGF-β
1-induced nuclear accumulation of Smad3 and Smad4, and potentiated activated PSC proliferation. PKC inhibitor Go6983 blocked the induction of Smad7 mRNA expression by Ang II. In addition, 12-
O-tetradecanoyl-phorbol 13-acetate, a PKC activator, increased Smad7 mRNA expression. These results suggest that Ang II enhances activated PSC proliferation by blocking autocrine TGF-β
1-mediated growth inhibition by inducing Smad7 expression via a PKC-dependent pathway.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16380081</pmid><doi>10.1016/j.bbrc.2005.12.069</doi><tpages>9</tpages></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 2006-02, Vol.340 (3), p.742-750 |
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| subjects | 60 APPLIED LIFE SCIENCES ACETATES Adenoviridae - metabolism ADENOVIRUS ANGIOTENSIN Angiotensin II Angiotensin II - metabolism Angiotensin II - physiology Animals Blotting, Western Carbazoles - pharmacology Cell Nucleus - metabolism CELL PROLIFERATION Cells, Cultured DNA - metabolism Dose-Response Relationship, Drug Enzyme Activation Enzyme Inhibitors - pharmacology FIBROSIS Fibrosis - pathology GROWTH Immunohistochemistry Indoles INHIBITION Maleimides NF-kappa B - metabolism NF-κB OXYGEN 12 PANCREAS Pancreas - cytology Pancreas - metabolism Pancreas - pathology Pancreatic stellate cell Proliferation Protein kinase C Protein Kinase C - metabolism Rats Receptor, Epidermal Growth Factor - metabolism RECEPTORS RNA, Messenger - metabolism Signal Transduction Smad Smad3 Protein - metabolism Smad4 Protein - metabolism Smad7 Protein - metabolism Tetradecanoylphorbol Acetate - pharmacology TGF-β Time Factors Transcriptional Activation Transforming Growth Factor beta - metabolism Transforming Growth Factor beta1 |
| title | Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway |
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