Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration
Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2014-10, Vol.111 (41), p.14806-14811 |
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| creator | He, Chang Zhao, Chen Kumar, Anil Lee, Chunsik Chen, Mingquan Huang, Lijuan Wang, Jing Ren, Xiangrong Jiang, Yida Chen, Wei Wang, Bin Gao, Zhiqin Zhong, Zheng Huang, Zijing Zhang, Fan Huang, Bing Ding, Hao Ju, Rong Tang, Zhongshu Liu, Yizhi Cao, Yihai Li, Xuri Liu, Xialin |
| description | Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor. PDGF-CC deficiency by genetic deletion exacerbated blood vessel regression/degeneration in various animal models. Importantly, treatment with PDGF-CC protein not only increased the survival of retinal blood vessels in a model of oxygen-induced blood vessel regression but also markedly rescued retinal and blood vessel degeneration in a disease model of retinitis pigmentosa. Mechanistically, we revealed that heme oxygenase-1 (HMOX1) activity is critically required for the vascular protective/survival effect of PDGF-CC because blockade of HMOX1 completely abolished the protective effect of PDGF-CC in vitro and in vivo. We further found that both PDGF receptors, PDGFR-β and PDGFR-β, are required for the vasoprotective effect of PDGF-CC. Thus our data show that PDGF-CC plays a pivotal role in maintaining blood vessel survival and may be of therapeutic value in treating various types of degenerative diseases. |
| doi_str_mv | 10.1073/pnas.1404140111 |
| format | Article |
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Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor. PDGF-CC deficiency by genetic deletion exacerbated blood vessel regression/degeneration in various animal models. Importantly, treatment with PDGF-CC protein not only increased the survival of retinal blood vessels in a model of oxygen-induced blood vessel regression but also markedly rescued retinal and blood vessel degeneration in a disease model of retinitis pigmentosa. Mechanistically, we revealed that heme oxygenase-1 (HMOX1) activity is critically required for the vascular protective/survival effect of PDGF-CC because blockade of HMOX1 completely abolished the protective effect of PDGF-CC in vitro and in vivo. We further found that both PDGF receptors, PDGFR-β and PDGFR-β, are required for the vasoprotective effect of PDGF-CC. Thus our data show that PDGF-CC plays a pivotal role in maintaining blood vessel survival and may be of therapeutic value in treating various types of degenerative diseases.</description><identifier>ISSN: 0027-8424</identifier><identifier>ISSN: 1091-6490</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1404140111</identifier><identifier>PMID: 25267616</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Alzheimers disease ; Angiogenesis ; Animal models ; Animals ; Biological Sciences ; Blood vessels ; Cell culture ; Cell Survival - drug effects ; Disease Models, Animal ; Endothelial Cells - drug effects ; Endothelial Cells - pathology ; Eye diseases ; Heme Oxygenase-1 - metabolism ; Lymphokines - metabolism ; Lymphokines - pharmacology ; Medicin och hälsovetenskap ; Mice ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - pathology ; Nervous system diseases ; Oxygen ; Parkinson disease ; Pathology ; Platelet-Derived Growth Factor - metabolism ; Platelet-Derived Growth Factor - pharmacology ; Proteins ; Receptor, Platelet-Derived Growth Factor alpha - metabolism ; Receptor, Platelet-Derived Growth Factor beta - metabolism ; Receptors ; Retina ; Retinal degeneration ; Retinal Degeneration - enzymology ; Retinal Degeneration - pathology ; Retinal Degeneration - prevention & control ; Retinal Vessels - drug effects ; Retinal Vessels - enzymology ; Retinal Vessels - pathology ; Survival analysis ; Up-Regulation - drug effects ; Vascular diseases</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2014-10, Vol.111 (41), p.14806-14811</ispartof><rights>copyright © 1993–2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Oct 14, 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c655t-4a7f172767c5f5c6bc7c2276e7026a002dbde00d0a421ffa3f5bf1c7e8bca6b63</citedby><cites>FETCH-LOGICAL-c655t-4a7f172767c5f5c6bc7c2276e7026a002dbde00d0a421ffa3f5bf1c7e8bca6b63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/111/41.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/43190158$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/43190158$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,552,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25267616$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:129899902$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>He, Chang</creatorcontrib><creatorcontrib>Zhao, Chen</creatorcontrib><creatorcontrib>Kumar, Anil</creatorcontrib><creatorcontrib>Lee, Chunsik</creatorcontrib><creatorcontrib>Chen, Mingquan</creatorcontrib><creatorcontrib>Huang, Lijuan</creatorcontrib><creatorcontrib>Wang, Jing</creatorcontrib><creatorcontrib>Ren, Xiangrong</creatorcontrib><creatorcontrib>Jiang, Yida</creatorcontrib><creatorcontrib>Chen, Wei</creatorcontrib><creatorcontrib>Wang, Bin</creatorcontrib><creatorcontrib>Gao, Zhiqin</creatorcontrib><creatorcontrib>Zhong, Zheng</creatorcontrib><creatorcontrib>Huang, Zijing</creatorcontrib><creatorcontrib>Zhang, Fan</creatorcontrib><creatorcontrib>Huang, Bing</creatorcontrib><creatorcontrib>Ding, Hao</creatorcontrib><creatorcontrib>Ju, Rong</creatorcontrib><creatorcontrib>Tang, Zhongshu</creatorcontrib><creatorcontrib>Liu, Yizhi</creatorcontrib><creatorcontrib>Cao, Yihai</creatorcontrib><creatorcontrib>Li, Xuri</creatorcontrib><creatorcontrib>Liu, Xialin</creatorcontrib><title>Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor. PDGF-CC deficiency by genetic deletion exacerbated blood vessel regression/degeneration in various animal models. Importantly, treatment with PDGF-CC protein not only increased the survival of retinal blood vessels in a model of oxygen-induced blood vessel regression but also markedly rescued retinal and blood vessel degeneration in a disease model of retinitis pigmentosa. Mechanistically, we revealed that heme oxygenase-1 (HMOX1) activity is critically required for the vascular protective/survival effect of PDGF-CC because blockade of HMOX1 completely abolished the protective effect of PDGF-CC in vitro and in vivo. We further found that both PDGF receptors, PDGFR-β and PDGFR-β, are required for the vasoprotective effect of PDGF-CC. Thus our data show that PDGF-CC plays a pivotal role in maintaining blood vessel survival and may be of therapeutic value in treating various types of degenerative diseases.</description><subject>Alzheimers disease</subject><subject>Angiogenesis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Blood vessels</subject><subject>Cell culture</subject><subject>Cell Survival - drug effects</subject><subject>Disease Models, Animal</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - pathology</subject><subject>Eye diseases</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Lymphokines - metabolism</subject><subject>Lymphokines - pharmacology</subject><subject>Medicin och hälsovetenskap</subject><subject>Mice</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - pathology</subject><subject>Nervous system diseases</subject><subject>Oxygen</subject><subject>Parkinson disease</subject><subject>Pathology</subject><subject>Platelet-Derived Growth Factor - metabolism</subject><subject>Platelet-Derived Growth Factor - pharmacology</subject><subject>Proteins</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - metabolism</subject><subject>Receptor, Platelet-Derived Growth Factor beta - metabolism</subject><subject>Receptors</subject><subject>Retina</subject><subject>Retinal degeneration</subject><subject>Retinal Degeneration - enzymology</subject><subject>Retinal Degeneration - pathology</subject><subject>Retinal Degeneration - prevention & control</subject><subject>Retinal Vessels - drug effects</subject><subject>Retinal Vessels - enzymology</subject><subject>Retinal Vessels - pathology</subject><subject>Survival analysis</subject><subject>Up-Regulation - drug effects</subject><subject>Vascular diseases</subject><issn>0027-8424</issn><issn>1091-6490</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp1kk1v1DAQhi0EokvhzAkUiQuXtDOOP5ILElpoi1S0HABxsxzHLll2462dLeq_Z6LdbikSB2v88byvx-Nh7CXCCYKuTjeDzScoQNBAxEdshtBgqUQDj9kMgOuyFlwcsWc5LwGgkTU8ZUdccqUVqhlbfLc5blIcvRv7G1_4EGhWxFB8-XB-Vs7nxdp3vR19V7S3xcXnxQ8sks9u6zPFsR_squj8lR98smMfh-fsSbCr7F_s4zH7dvbx6_yivFycf5q_vyydknIshdUBNddKOxmkU63TjtPSa-DKUt5d23mADqzgGIKtgmwDOu3r1lnVquqYlTvf_Ntvtq3ZpH5t062Jtjf7rV8080ZiLRUS3_yXp-d396I7IfKmbpoGOGnf7bQEUDWcH8ZkVw8tHpwM_U9zFW-M4EB3Axm83RukeE2VG826z86vVnbwcZsNKs7pN7ioCX3zD7qM20RVniisJDZcSqJOd5RLMefkwyEZBDM1hpkaw9w3Bile__2GA3_XCQQUe2BSHuwQjUAyqmFCXu2QZR5jOjCiwgZQ1tUf6XvJcQ</recordid><startdate>20141014</startdate><enddate>20141014</enddate><creator>He, Chang</creator><creator>Zhao, Chen</creator><creator>Kumar, Anil</creator><creator>Lee, Chunsik</creator><creator>Chen, Mingquan</creator><creator>Huang, Lijuan</creator><creator>Wang, Jing</creator><creator>Ren, Xiangrong</creator><creator>Jiang, Yida</creator><creator>Chen, Wei</creator><creator>Wang, Bin</creator><creator>Gao, Zhiqin</creator><creator>Zhong, Zheng</creator><creator>Huang, Zijing</creator><creator>Zhang, Fan</creator><creator>Huang, Bing</creator><creator>Ding, Hao</creator><creator>Ju, Rong</creator><creator>Tang, Zhongshu</creator><creator>Liu, Yizhi</creator><creator>Cao, Yihai</creator><creator>Li, Xuri</creator><creator>Liu, Xialin</creator><general>National Academy of Sciences</general><general>National Acad Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20141014</creationdate><title>Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration</title><author>He, Chang ; Zhao, Chen ; Kumar, Anil ; Lee, Chunsik ; Chen, Mingquan ; Huang, Lijuan ; Wang, Jing ; Ren, Xiangrong ; Jiang, Yida ; Chen, Wei ; Wang, Bin ; Gao, Zhiqin ; Zhong, Zheng ; Huang, Zijing ; Zhang, Fan ; Huang, Bing ; Ding, Hao ; Ju, Rong ; Tang, Zhongshu ; Liu, Yizhi ; Cao, Yihai ; Li, Xuri ; Liu, Xialin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c655t-4a7f172767c5f5c6bc7c2276e7026a002dbde00d0a421ffa3f5bf1c7e8bca6b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Alzheimers disease</topic><topic>Angiogenesis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biological Sciences</topic><topic>Blood vessels</topic><topic>Cell culture</topic><topic>Cell Survival - drug effects</topic><topic>Disease Models, Animal</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - pathology</topic><topic>Eye diseases</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>Lymphokines - metabolism</topic><topic>Lymphokines - pharmacology</topic><topic>Medicin och hälsovetenskap</topic><topic>Mice</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - pathology</topic><topic>Nervous system diseases</topic><topic>Oxygen</topic><topic>Parkinson disease</topic><topic>Pathology</topic><topic>Platelet-Derived Growth Factor - metabolism</topic><topic>Platelet-Derived Growth Factor - pharmacology</topic><topic>Proteins</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - metabolism</topic><topic>Receptor, Platelet-Derived Growth Factor beta - metabolism</topic><topic>Receptors</topic><topic>Retina</topic><topic>Retinal degeneration</topic><topic>Retinal Degeneration - enzymology</topic><topic>Retinal Degeneration - pathology</topic><topic>Retinal Degeneration - prevention & control</topic><topic>Retinal Vessels - drug effects</topic><topic>Retinal Vessels - enzymology</topic><topic>Retinal Vessels - pathology</topic><topic>Survival analysis</topic><topic>Up-Regulation - drug effects</topic><topic>Vascular diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, Chang</creatorcontrib><creatorcontrib>Zhao, Chen</creatorcontrib><creatorcontrib>Kumar, Anil</creatorcontrib><creatorcontrib>Lee, Chunsik</creatorcontrib><creatorcontrib>Chen, Mingquan</creatorcontrib><creatorcontrib>Huang, Lijuan</creatorcontrib><creatorcontrib>Wang, Jing</creatorcontrib><creatorcontrib>Ren, Xiangrong</creatorcontrib><creatorcontrib>Jiang, Yida</creatorcontrib><creatorcontrib>Chen, Wei</creatorcontrib><creatorcontrib>Wang, Bin</creatorcontrib><creatorcontrib>Gao, Zhiqin</creatorcontrib><creatorcontrib>Zhong, Zheng</creatorcontrib><creatorcontrib>Huang, Zijing</creatorcontrib><creatorcontrib>Zhang, Fan</creatorcontrib><creatorcontrib>Huang, Bing</creatorcontrib><creatorcontrib>Ding, Hao</creatorcontrib><creatorcontrib>Ju, Rong</creatorcontrib><creatorcontrib>Tang, Zhongshu</creatorcontrib><creatorcontrib>Liu, Yizhi</creatorcontrib><creatorcontrib>Cao, Yihai</creatorcontrib><creatorcontrib>Li, Xuri</creatorcontrib><creatorcontrib>Liu, Xialin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>He, Chang</au><au>Zhao, Chen</au><au>Kumar, Anil</au><au>Lee, Chunsik</au><au>Chen, Mingquan</au><au>Huang, Lijuan</au><au>Wang, Jing</au><au>Ren, Xiangrong</au><au>Jiang, Yida</au><au>Chen, Wei</au><au>Wang, Bin</au><au>Gao, Zhiqin</au><au>Zhong, Zheng</au><au>Huang, Zijing</au><au>Zhang, Fan</au><au>Huang, Bing</au><au>Ding, Hao</au><au>Ju, Rong</au><au>Tang, Zhongshu</au><au>Liu, Yizhi</au><au>Cao, Yihai</au><au>Li, Xuri</au><au>Liu, Xialin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2014-10-14</date><risdate>2014</risdate><volume>111</volume><issue>41</issue><spage>14806</spage><epage>14811</epage><pages>14806-14811</pages><issn>0027-8424</issn><issn>1091-6490</issn><eissn>1091-6490</eissn><abstract>Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor. PDGF-CC deficiency by genetic deletion exacerbated blood vessel regression/degeneration in various animal models. Importantly, treatment with PDGF-CC protein not only increased the survival of retinal blood vessels in a model of oxygen-induced blood vessel regression but also markedly rescued retinal and blood vessel degeneration in a disease model of retinitis pigmentosa. Mechanistically, we revealed that heme oxygenase-1 (HMOX1) activity is critically required for the vascular protective/survival effect of PDGF-CC because blockade of HMOX1 completely abolished the protective effect of PDGF-CC in vitro and in vivo. We further found that both PDGF receptors, PDGFR-β and PDGFR-β, are required for the vasoprotective effect of PDGF-CC. Thus our data show that PDGF-CC plays a pivotal role in maintaining blood vessel survival and may be of therapeutic value in treating various types of degenerative diseases.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>25267616</pmid><doi>10.1073/pnas.1404140111</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2014-10, Vol.111 (41), p.14806-14811 |
| issn | 0027-8424 1091-6490 1091-6490 |
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| source | MEDLINE; SWEPUB Freely available online; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Alzheimers disease Angiogenesis Animal models Animals Biological Sciences Blood vessels Cell culture Cell Survival - drug effects Disease Models, Animal Endothelial Cells - drug effects Endothelial Cells - pathology Eye diseases Heme Oxygenase-1 - metabolism Lymphokines - metabolism Lymphokines - pharmacology Medicin och hälsovetenskap Mice Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - pathology Nervous system diseases Oxygen Parkinson disease Pathology Platelet-Derived Growth Factor - metabolism Platelet-Derived Growth Factor - pharmacology Proteins Receptor, Platelet-Derived Growth Factor alpha - metabolism Receptor, Platelet-Derived Growth Factor beta - metabolism Receptors Retina Retinal degeneration Retinal Degeneration - enzymology Retinal Degeneration - pathology Retinal Degeneration - prevention & control Retinal Vessels - drug effects Retinal Vessels - enzymology Retinal Vessels - pathology Survival analysis Up-Regulation - drug effects Vascular diseases |
| title | Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration |
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