The pericyte as a cellular regulator of penile erection and a novel therapeutic target for erectile dysfunction
Pericytes are known to play critical roles in vascular development and homeostasis. However, the distribution of cavernous pericytes and their roles in penile erection is unclear. Herein we report that the pericytes are abundantly distributed in microvessels of the subtunical area and dorsal nerve b...
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| Veröffentlicht in: | Scientific reports 2015-06, Vol.5 (1), p.10891-10891, Article 10891 |
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| creator | Yin, Guo Nan Das, Nando Dulal Choi, Min Ji Song, Kang-Moon Kwon, Mi-Hye Ock, Jiyeon Limanjaya, Anita Ghatak, Kalyan Kim, Woo Jean Hyun, Jae Seog Koh, Gou Young Ryu, Ji-Kan Suh, Jun-Kyu |
| description | Pericytes are known to play critical roles in vascular development and homeostasis. However, the distribution of cavernous pericytes and their roles in penile erection is unclear. Herein we report that the pericytes are abundantly distributed in microvessels of the subtunical area and dorsal nerve bundle of mice, followed by dorsal vein and cavernous sinusoids. We further confirmed the presence of pericytes in human corpus cavernosum tissue and successfully isolated pericytes from mouse penis. Cavernous pericyte contents from diabetic mice and tube formation of cultured pericytes in high glucose condition were greatly reduced compared with those in normal conditions. Suppression of pericyte function with anti-PDGFR-β blocking antibody deteriorated erectile function and tube formation
in vivo
and
in vitro
diabetic condition. In contrast, enhanced pericyte function with HGF protein restored cavernous pericyte content in diabetic mice and significantly decreased cavernous permeability in diabetic mice and in pericytes-endothelial cell co-culture system, which induced significant recovery of erectile function. Overall, these findings showed the presence and distribution of pericytes in the penis of normal or pathologic condition and documented their role in the regulation of cavernous permeability and penile erection, which ultimately explore novel therapeutics of erectile dysfunction targeting pericyte function. |
| doi_str_mv | 10.1038/srep10891 |
| format | Article |
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in vivo
and
in vitro
diabetic condition. In contrast, enhanced pericyte function with HGF protein restored cavernous pericyte content in diabetic mice and significantly decreased cavernous permeability in diabetic mice and in pericytes-endothelial cell co-culture system, which induced significant recovery of erectile function. Overall, these findings showed the presence and distribution of pericytes in the penis of normal or pathologic condition and documented their role in the regulation of cavernous permeability and penile erection, which ultimately explore novel therapeutics of erectile dysfunction targeting pericyte function.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep10891</identifier><identifier>PMID: 26044953</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/106 ; 14/19 ; 38/1 ; 631/80/2373 ; 631/80/86 ; 64/60 ; Androgens ; Animals ; Antibodies, Monoclonal - pharmacology ; Biomarkers ; Cell culture ; Cell Separation ; Coculture Techniques ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Experimental ; Disease Models, Animal ; Endothelial Cells - metabolism ; Erectile dysfunction ; Erectile Dysfunction - metabolism ; Erectile Dysfunction - physiopathology ; Hepatocyte Growth Factor - pharmacology ; Homeostasis ; Humanities and Social Sciences ; Humans ; Male ; Mice ; multidisciplinary ; Penile Erection - drug effects ; Penile Erection - physiology ; Penis ; Penis - cytology ; Pericytes ; Pericytes - cytology ; Pericytes - drug effects ; Pericytes - metabolism ; Permeability ; Receptor, Platelet-Derived Growth Factor beta - antagonists & inhibitors ; Receptor, Platelet-Derived Growth Factor beta - metabolism ; Rodents ; Science</subject><ispartof>Scientific reports, 2015-06, Vol.5 (1), p.10891-10891, Article 10891</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Jun 2015</rights><rights>Copyright © 2015, Macmillan Publishers Limited 2015 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-5705041613cd6dc224adeabc68e5720d82597b97dc42db5237206c92becaa58b3</citedby><cites>FETCH-LOGICAL-c504t-5705041613cd6dc224adeabc68e5720d82597b97dc42db5237206c92becaa58b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456662/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456662/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26044953$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yin, Guo Nan</creatorcontrib><creatorcontrib>Das, Nando Dulal</creatorcontrib><creatorcontrib>Choi, Min Ji</creatorcontrib><creatorcontrib>Song, Kang-Moon</creatorcontrib><creatorcontrib>Kwon, Mi-Hye</creatorcontrib><creatorcontrib>Ock, Jiyeon</creatorcontrib><creatorcontrib>Limanjaya, Anita</creatorcontrib><creatorcontrib>Ghatak, Kalyan</creatorcontrib><creatorcontrib>Kim, Woo Jean</creatorcontrib><creatorcontrib>Hyun, Jae Seog</creatorcontrib><creatorcontrib>Koh, Gou Young</creatorcontrib><creatorcontrib>Ryu, Ji-Kan</creatorcontrib><creatorcontrib>Suh, Jun-Kyu</creatorcontrib><title>The pericyte as a cellular regulator of penile erection and a novel therapeutic target for erectile dysfunction</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Pericytes are known to play critical roles in vascular development and homeostasis. However, the distribution of cavernous pericytes and their roles in penile erection is unclear. Herein we report that the pericytes are abundantly distributed in microvessels of the subtunical area and dorsal nerve bundle of mice, followed by dorsal vein and cavernous sinusoids. We further confirmed the presence of pericytes in human corpus cavernosum tissue and successfully isolated pericytes from mouse penis. Cavernous pericyte contents from diabetic mice and tube formation of cultured pericytes in high glucose condition were greatly reduced compared with those in normal conditions. Suppression of pericyte function with anti-PDGFR-β blocking antibody deteriorated erectile function and tube formation
in vivo
and
in vitro
diabetic condition. In contrast, enhanced pericyte function with HGF protein restored cavernous pericyte content in diabetic mice and significantly decreased cavernous permeability in diabetic mice and in pericytes-endothelial cell co-culture system, which induced significant recovery of erectile function. Overall, these findings showed the presence and distribution of pericytes in the penis of normal or pathologic condition and documented their role in the regulation of cavernous permeability and penile erection, which ultimately explore novel therapeutics of erectile dysfunction targeting pericyte function.</description><subject>13/106</subject><subject>14/19</subject><subject>38/1</subject><subject>631/80/2373</subject><subject>631/80/86</subject><subject>64/60</subject><subject>Androgens</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Biomarkers</subject><subject>Cell culture</subject><subject>Cell Separation</subject><subject>Coculture Techniques</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental</subject><subject>Disease Models, Animal</subject><subject>Endothelial Cells - metabolism</subject><subject>Erectile dysfunction</subject><subject>Erectile Dysfunction - metabolism</subject><subject>Erectile Dysfunction - physiopathology</subject><subject>Hepatocyte Growth Factor - pharmacology</subject><subject>Homeostasis</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>multidisciplinary</subject><subject>Penile Erection - drug effects</subject><subject>Penile Erection - physiology</subject><subject>Penis</subject><subject>Penis - cytology</subject><subject>Pericytes</subject><subject>Pericytes - cytology</subject><subject>Pericytes - drug effects</subject><subject>Pericytes - metabolism</subject><subject>Permeability</subject><subject>Receptor, Platelet-Derived Growth Factor beta - antagonists & inhibitors</subject><subject>Receptor, Platelet-Derived Growth Factor beta - metabolism</subject><subject>Rodents</subject><subject>Science</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkVFrHCEUhaW0NCHNQ_9AEPLSFrZVR93xJRBC0hQCfUmfxdE7uxNmdaJOYP99b7rpsml9OeL97vHqIeQjZ185a9pvJcPEWWv4G3IsmFQL0Qjx9mB_RE5LeWC4lDCSm_fkSGgmpVHNMUn3a6AT5MFvK1BXqKMexnEeXaYZVqg1ZZp6ZOIwAoUMvg4pUhcDsjE9wUjrGrKbYK6Dp9XlFVTaY9eOxaawLf0c__R9IO96NxY4fdET8uvm-v7qdnH38_uPq8u7hVdM1oVaMlSueeODDl4I6QK4zusW1FKw0Apllp1ZBi9F6JRo8FB7Izrwzqm2a07Ixc53mrsNBA-xZjfaKQ8bl7c2ucG-rsRhbVfpyUqptNYCDT69GOT0OEOpdjOU569xEdJcLNetNqY1RiJ6_g_6kOYc8XmWI6A0M0Ih9XlH-ZwKhtbvh-HMPidp90kie3Y4_Z78mxsCX3ZAwVJcQT648j-332H7qZg</recordid><startdate>20150605</startdate><enddate>20150605</enddate><creator>Yin, Guo Nan</creator><creator>Das, Nando Dulal</creator><creator>Choi, Min Ji</creator><creator>Song, Kang-Moon</creator><creator>Kwon, Mi-Hye</creator><creator>Ock, Jiyeon</creator><creator>Limanjaya, Anita</creator><creator>Ghatak, Kalyan</creator><creator>Kim, Woo Jean</creator><creator>Hyun, Jae Seog</creator><creator>Koh, Gou Young</creator><creator>Ryu, Ji-Kan</creator><creator>Suh, Jun-Kyu</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150605</creationdate><title>The pericyte as a cellular regulator of penile erection and a novel therapeutic target for erectile dysfunction</title><author>Yin, Guo Nan ; Das, Nando Dulal ; Choi, Min Ji ; Song, Kang-Moon ; Kwon, Mi-Hye ; Ock, Jiyeon ; Limanjaya, Anita ; Ghatak, Kalyan ; Kim, Woo Jean ; Hyun, Jae Seog ; Koh, Gou Young ; Ryu, Ji-Kan ; Suh, Jun-Kyu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-5705041613cd6dc224adeabc68e5720d82597b97dc42db5237206c92becaa58b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>13/106</topic><topic>14/19</topic><topic>38/1</topic><topic>631/80/2373</topic><topic>631/80/86</topic><topic>64/60</topic><topic>Androgens</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Biomarkers</topic><topic>Cell culture</topic><topic>Cell Separation</topic><topic>Coculture Techniques</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Experimental</topic><topic>Disease Models, Animal</topic><topic>Endothelial Cells - metabolism</topic><topic>Erectile dysfunction</topic><topic>Erectile Dysfunction - metabolism</topic><topic>Erectile Dysfunction - physiopathology</topic><topic>Hepatocyte Growth Factor - pharmacology</topic><topic>Homeostasis</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>multidisciplinary</topic><topic>Penile Erection - drug effects</topic><topic>Penile Erection - physiology</topic><topic>Penis</topic><topic>Penis - cytology</topic><topic>Pericytes</topic><topic>Pericytes - cytology</topic><topic>Pericytes - drug effects</topic><topic>Pericytes - metabolism</topic><topic>Permeability</topic><topic>Receptor, Platelet-Derived Growth Factor beta - antagonists & inhibitors</topic><topic>Receptor, Platelet-Derived Growth Factor beta - metabolism</topic><topic>Rodents</topic><topic>Science</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yin, Guo Nan</creatorcontrib><creatorcontrib>Das, Nando Dulal</creatorcontrib><creatorcontrib>Choi, Min Ji</creatorcontrib><creatorcontrib>Song, Kang-Moon</creatorcontrib><creatorcontrib>Kwon, Mi-Hye</creatorcontrib><creatorcontrib>Ock, Jiyeon</creatorcontrib><creatorcontrib>Limanjaya, Anita</creatorcontrib><creatorcontrib>Ghatak, Kalyan</creatorcontrib><creatorcontrib>Kim, Woo Jean</creatorcontrib><creatorcontrib>Hyun, Jae Seog</creatorcontrib><creatorcontrib>Koh, Gou Young</creatorcontrib><creatorcontrib>Ryu, Ji-Kan</creatorcontrib><creatorcontrib>Suh, Jun-Kyu</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yin, Guo Nan</au><au>Das, Nando Dulal</au><au>Choi, Min Ji</au><au>Song, Kang-Moon</au><au>Kwon, Mi-Hye</au><au>Ock, Jiyeon</au><au>Limanjaya, Anita</au><au>Ghatak, Kalyan</au><au>Kim, Woo Jean</au><au>Hyun, Jae Seog</au><au>Koh, Gou Young</au><au>Ryu, Ji-Kan</au><au>Suh, Jun-Kyu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The pericyte as a cellular regulator of penile erection and a novel therapeutic target for erectile dysfunction</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2015-06-05</date><risdate>2015</risdate><volume>5</volume><issue>1</issue><spage>10891</spage><epage>10891</epage><pages>10891-10891</pages><artnum>10891</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Pericytes are known to play critical roles in vascular development and homeostasis. However, the distribution of cavernous pericytes and their roles in penile erection is unclear. Herein we report that the pericytes are abundantly distributed in microvessels of the subtunical area and dorsal nerve bundle of mice, followed by dorsal vein and cavernous sinusoids. We further confirmed the presence of pericytes in human corpus cavernosum tissue and successfully isolated pericytes from mouse penis. Cavernous pericyte contents from diabetic mice and tube formation of cultured pericytes in high glucose condition were greatly reduced compared with those in normal conditions. Suppression of pericyte function with anti-PDGFR-β blocking antibody deteriorated erectile function and tube formation
in vivo
and
in vitro
diabetic condition. In contrast, enhanced pericyte function with HGF protein restored cavernous pericyte content in diabetic mice and significantly decreased cavernous permeability in diabetic mice and in pericytes-endothelial cell co-culture system, which induced significant recovery of erectile function. Overall, these findings showed the presence and distribution of pericytes in the penis of normal or pathologic condition and documented their role in the regulation of cavernous permeability and penile erection, which ultimately explore novel therapeutics of erectile dysfunction targeting pericyte function.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26044953</pmid><doi>10.1038/srep10891</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/106 14/19 38/1 631/80/2373 631/80/86 64/60 Androgens Animals Antibodies, Monoclonal - pharmacology Biomarkers Cell culture Cell Separation Coculture Techniques Diabetes Diabetes mellitus Diabetes Mellitus, Experimental Disease Models, Animal Endothelial Cells - metabolism Erectile dysfunction Erectile Dysfunction - metabolism Erectile Dysfunction - physiopathology Hepatocyte Growth Factor - pharmacology Homeostasis Humanities and Social Sciences Humans Male Mice multidisciplinary Penile Erection - drug effects Penile Erection - physiology Penis Penis - cytology Pericytes Pericytes - cytology Pericytes - drug effects Pericytes - metabolism Permeability Receptor, Platelet-Derived Growth Factor beta - antagonists & inhibitors Receptor, Platelet-Derived Growth Factor beta - metabolism Rodents Science |
| title | The pericyte as a cellular regulator of penile erection and a novel therapeutic target for erectile dysfunction |
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