Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta
Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 an...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2016-04, Vol.473 (2), p.517-523 |
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| container_title | Biochemical and biophysical research communications |
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| creator | He, Rui-Qing Tang, Xiao-Feng Zhang, Bao-Li Li, Xiao-Dong Hong, Mo-Na Chen, Qi-Zhi Han, Wei-Qing Gao, Ping-Jin |
| description | Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes.
•Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation.•PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation.•Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs. |
| doi_str_mv | 10.1016/j.bbrc.2016.03.094 |
| format | Article |
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•Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation.•PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation.•Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2016.03.094</identifier><identifier>PMID: 27012211</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Adventitial fibroblast ; Adventitial remodeling ; ANGIOTENSIN ; Angiotensin II ; Angiotensin II - metabolism ; Animals ; AORTA ; Aorta - cytology ; Aorta - drug effects ; Aorta - metabolism ; BIOSYNTHESIS ; Cell Movement - drug effects ; CELL PROLIFERATION ; Cell Proliferation - drug effects ; Cells, Cultured ; FIBROBLASTS ; Fibroblasts - cytology ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; INFLAMMATION ; LYMPHOKINES ; Male ; MAP Kinase Signaling System - drug effects ; Protease-activated receptor ; RATS ; Rats, Sprague-Dawley ; Receptor, PAR-1 - agonists ; Receptor, PAR-1 - antagonists & inhibitors ; Receptor, PAR-1 - metabolism ; Receptor, PAR-2 - agonists ; Receptor, PAR-2 - antagonists & inhibitors ; Receptor, PAR-2 - metabolism ; RECEPTORS</subject><ispartof>Biochemical and biophysical research communications, 2016-04, Vol.473 (2), p.517-523</ispartof><rights>2016</rights><rights>Copyright © 2016. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-da0c4d059d209626fa7b65edc320a9cbf3cdd9186f40582ead581b094281c11d3</citedby><cites>FETCH-LOGICAL-c450t-da0c4d059d209626fa7b65edc320a9cbf3cdd9186f40582ead581b094281c11d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X16304053$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27012211$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22596363$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>He, Rui-Qing</creatorcontrib><creatorcontrib>Tang, Xiao-Feng</creatorcontrib><creatorcontrib>Zhang, Bao-Li</creatorcontrib><creatorcontrib>Li, Xiao-Dong</creatorcontrib><creatorcontrib>Hong, Mo-Na</creatorcontrib><creatorcontrib>Chen, Qi-Zhi</creatorcontrib><creatorcontrib>Han, Wei-Qing</creatorcontrib><creatorcontrib>Gao, Ping-Jin</creatorcontrib><title>Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes.
•Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation.•PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation.•Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Adventitial fibroblast</subject><subject>Adventitial remodeling</subject><subject>ANGIOTENSIN</subject><subject>Angiotensin II</subject><subject>Angiotensin II - metabolism</subject><subject>Animals</subject><subject>AORTA</subject><subject>Aorta - cytology</subject><subject>Aorta - drug effects</subject><subject>Aorta - metabolism</subject><subject>BIOSYNTHESIS</subject><subject>Cell Movement - drug effects</subject><subject>CELL PROLIFERATION</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>FIBROBLASTS</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>INFLAMMATION</subject><subject>LYMPHOKINES</subject><subject>Male</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Protease-activated receptor</subject><subject>RATS</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, PAR-1 - agonists</subject><subject>Receptor, PAR-1 - antagonists & inhibitors</subject><subject>Receptor, PAR-1 - metabolism</subject><subject>Receptor, PAR-2 - agonists</subject><subject>Receptor, PAR-2 - antagonists & inhibitors</subject><subject>Receptor, PAR-2 - metabolism</subject><subject>RECEPTORS</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUuLFDEUhYMoTjv6B1xIwI2bKu9NPboK3MjgjA0DuhjBXcjjlqapTtok1TAL_7spunXpKiF853ByDmOvEWoE7N_va62jqUW519DUMLZP2AZhhEogtE_ZBgD6Soz4_Yq9SGkPgNj243N2JbaAQiBu2O-vMWRSiSplsjupTJZHMnTMIXLkylsuuAk-R6eXTDyH8vbDFY1PzvPdrnLeLqaoLnoXPA8TV_ZEPrvs1Mwnp2PQs0o58SmGA48qcxViVi_Zs0nNiV5dzmv27fbTw83n6v7L3e7m431l2g5yZRWY1kI3WgFjL_pJbXXfkTWNADUaPTXG2hGHfmqhGwQp2w2oSx9iQINom2v29uwbUnYyGZfJ_Cy_8mSyFKIb-6ZvCvXuTB1j-LVQyvLgkqF5Vp7CkiRuh1Jat4W2oOKMmhhSijTJY3QHFR8lglzHkXu5jiPXcSQ0soQpojcX_0UfyP6T_F2jAB_OAJUuTo7iGpV8adfFNakN7n_-fwBjvqFL</recordid><startdate>20160429</startdate><enddate>20160429</enddate><creator>He, Rui-Qing</creator><creator>Tang, Xiao-Feng</creator><creator>Zhang, Bao-Li</creator><creator>Li, Xiao-Dong</creator><creator>Hong, Mo-Na</creator><creator>Chen, Qi-Zhi</creator><creator>Han, Wei-Qing</creator><creator>Gao, Ping-Jin</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>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20160429</creationdate><title>Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta</title><author>He, Rui-Qing ; Tang, Xiao-Feng ; Zhang, Bao-Li ; Li, Xiao-Dong ; Hong, Mo-Na ; Chen, Qi-Zhi ; Han, Wei-Qing ; Gao, Ping-Jin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-da0c4d059d209626fa7b65edc320a9cbf3cdd9186f40582ead581b094281c11d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Adventitial fibroblast</topic><topic>Adventitial remodeling</topic><topic>ANGIOTENSIN</topic><topic>Angiotensin II</topic><topic>Angiotensin II - metabolism</topic><topic>Animals</topic><topic>AORTA</topic><topic>Aorta - cytology</topic><topic>Aorta - drug effects</topic><topic>Aorta - metabolism</topic><topic>BIOSYNTHESIS</topic><topic>Cell Movement - drug effects</topic><topic>CELL PROLIFERATION</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>FIBROBLASTS</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>INFLAMMATION</topic><topic>LYMPHOKINES</topic><topic>Male</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Protease-activated receptor</topic><topic>RATS</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, PAR-1 - agonists</topic><topic>Receptor, PAR-1 - antagonists & inhibitors</topic><topic>Receptor, PAR-1 - metabolism</topic><topic>Receptor, PAR-2 - agonists</topic><topic>Receptor, PAR-2 - antagonists & inhibitors</topic><topic>Receptor, PAR-2 - metabolism</topic><topic>RECEPTORS</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, Rui-Qing</creatorcontrib><creatorcontrib>Tang, Xiao-Feng</creatorcontrib><creatorcontrib>Zhang, Bao-Li</creatorcontrib><creatorcontrib>Li, Xiao-Dong</creatorcontrib><creatorcontrib>Hong, Mo-Na</creatorcontrib><creatorcontrib>Chen, Qi-Zhi</creatorcontrib><creatorcontrib>Han, Wei-Qing</creatorcontrib><creatorcontrib>Gao, Ping-Jin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</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>He, Rui-Qing</au><au>Tang, Xiao-Feng</au><au>Zhang, Bao-Li</au><au>Li, Xiao-Dong</au><au>Hong, Mo-Na</au><au>Chen, Qi-Zhi</au><au>Han, Wei-Qing</au><au>Gao, Ping-Jin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2016-04-29</date><risdate>2016</risdate><volume>473</volume><issue>2</issue><spage>517</spage><epage>523</epage><pages>517-523</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes.
•Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation.•PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation.•Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27012211</pmid><doi>10.1016/j.bbrc.2016.03.094</doi><tpages>7</tpages></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES Adventitial fibroblast Adventitial remodeling ANGIOTENSIN Angiotensin II Angiotensin II - metabolism Animals AORTA Aorta - cytology Aorta - drug effects Aorta - metabolism BIOSYNTHESIS Cell Movement - drug effects CELL PROLIFERATION Cell Proliferation - drug effects Cells, Cultured FIBROBLASTS Fibroblasts - cytology Fibroblasts - drug effects Fibroblasts - metabolism INFLAMMATION LYMPHOKINES Male MAP Kinase Signaling System - drug effects Protease-activated receptor RATS Rats, Sprague-Dawley Receptor, PAR-1 - agonists Receptor, PAR-1 - antagonists & inhibitors Receptor, PAR-1 - metabolism Receptor, PAR-2 - agonists Receptor, PAR-2 - antagonists & inhibitors Receptor, PAR-2 - metabolism RECEPTORS |
| title | Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta |
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