20-HETE Mediates Proliferation of Renal Epithelial Cells in Polycystic Kidney Disease
Polycystic kidney diseases are characterized by abnormal proliferation of renal epithelial cells. In this study, the role of 20-hydroxyeicosatetraenoic acid (20-HETE), an endogenous cytochrome P450 metabolite of arachidonic acid with mitogenic properties, was evaluated in cystic renal disease. Daily...
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| Veröffentlicht in: | Journal of the American Society of Nephrology 2008-10, Vol.19 (10), p.1929-1939 |
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| container_end_page | 1939 |
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| container_issue | 10 |
| container_start_page | 1929 |
| container_title | Journal of the American Society of Nephrology |
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| creator | PARK, Frank SWEENEY, William E GUANGFU JIA ROMAN, Richard J AVNER, Ellis D |
| description | Polycystic kidney diseases are characterized by abnormal proliferation of renal epithelial cells. In this study, the role of 20-hydroxyeicosatetraenoic acid (20-HETE), an endogenous cytochrome P450 metabolite of arachidonic acid with mitogenic properties, was evaluated in cystic renal disease. Daily administration of HET-0016, an inhibitor of 20-HETE synthesis, significantly reduced kidney size by half in the BPK mouse model of autosomal recessive polycystic kidney disease. In addition, compared with untreated BPK mice, this treatment significantly reduced collecting tubule cystic indices and approximately doubled survival. For evaluation of the role of 20-HETE as a mediator of epithelial cell proliferation, principal cells isolated from cystic BPK and noncystic Balb/c mice were genetically modified using lentiviral vectors. Noncystic Balb/c cells overproducing Cyp4a12 exhibited a four- to five-fold increase in cell proliferation compared with control Balb/c cells, and this increase was completely abolished when 20-HETE synthesis was inhibited; therefore, this study suggests that 20-HETE mediates proliferation of epithelial cells in the formation of renal cysts. |
| doi_str_mv | 10.1681/asn.2007070771 |
| format | Article |
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In this study, the role of 20-hydroxyeicosatetraenoic acid (20-HETE), an endogenous cytochrome P450 metabolite of arachidonic acid with mitogenic properties, was evaluated in cystic renal disease. Daily administration of HET-0016, an inhibitor of 20-HETE synthesis, significantly reduced kidney size by half in the BPK mouse model of autosomal recessive polycystic kidney disease. In addition, compared with untreated BPK mice, this treatment significantly reduced collecting tubule cystic indices and approximately doubled survival. For evaluation of the role of 20-HETE as a mediator of epithelial cell proliferation, principal cells isolated from cystic BPK and noncystic Balb/c mice were genetically modified using lentiviral vectors. Noncystic Balb/c cells overproducing Cyp4a12 exhibited a four- to five-fold increase in cell proliferation compared with control Balb/c cells, and this increase was completely abolished when 20-HETE synthesis was inhibited; therefore, this study suggests that 20-HETE mediates proliferation of epithelial cells in the formation of renal cysts.</description><identifier>ISSN: 1046-6673</identifier><identifier>EISSN: 1533-3450</identifier><identifier>DOI: 10.1681/asn.2007070771</identifier><identifier>PMID: 18596124</identifier><identifier>CODEN: JASNEU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Amidines - pharmacology ; Animals ; Basic Research ; Biological and medical sciences ; Cell Culture Techniques ; Cell Proliferation - drug effects ; Cytochrome P-450 Enzyme System - metabolism ; Cytochrome P-450 Enzyme System - physiology ; Cytochrome P450 Family 4 ; Disease Models, Animal ; Epithelial Cells - physiology ; Hydroxyeicosatetraenoic Acids - antagonists & inhibitors ; Hydroxyeicosatetraenoic Acids - physiology ; Kidneys ; Malformations of the urinary system ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Nephrology. Urinary tract diseases ; Polycystic Kidney Diseases - etiology ; Polycystic Kidney Diseases - metabolism ; Polycystic Kidney Diseases - pathology</subject><ispartof>Journal of the American Society of Nephrology, 2008-10, Vol.19 (10), p.1929-1939</ispartof><rights>2008 INIST-CNRS</rights><rights>Copyright © 2008 by the American Society of Nephrology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-17756f922d23ea85cf2052b351c789477bea7da82f7931122dbea5a1c71a2d443</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551562/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551562/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20715545$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18596124$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PARK, Frank</creatorcontrib><creatorcontrib>SWEENEY, William E</creatorcontrib><creatorcontrib>GUANGFU JIA</creatorcontrib><creatorcontrib>ROMAN, Richard J</creatorcontrib><creatorcontrib>AVNER, Ellis D</creatorcontrib><title>20-HETE Mediates Proliferation of Renal Epithelial Cells in Polycystic Kidney Disease</title><title>Journal of the American Society of Nephrology</title><addtitle>J Am Soc Nephrol</addtitle><description>Polycystic kidney diseases are characterized by abnormal proliferation of renal epithelial cells. In this study, the role of 20-hydroxyeicosatetraenoic acid (20-HETE), an endogenous cytochrome P450 metabolite of arachidonic acid with mitogenic properties, was evaluated in cystic renal disease. Daily administration of HET-0016, an inhibitor of 20-HETE synthesis, significantly reduced kidney size by half in the BPK mouse model of autosomal recessive polycystic kidney disease. In addition, compared with untreated BPK mice, this treatment significantly reduced collecting tubule cystic indices and approximately doubled survival. For evaluation of the role of 20-HETE as a mediator of epithelial cell proliferation, principal cells isolated from cystic BPK and noncystic Balb/c mice were genetically modified using lentiviral vectors. Noncystic Balb/c cells overproducing Cyp4a12 exhibited a four- to five-fold increase in cell proliferation compared with control Balb/c cells, and this increase was completely abolished when 20-HETE synthesis was inhibited; therefore, this study suggests that 20-HETE mediates proliferation of epithelial cells in the formation of renal cysts.</description><subject>Amidines - pharmacology</subject><subject>Animals</subject><subject>Basic Research</subject><subject>Biological and medical sciences</subject><subject>Cell Culture Techniques</subject><subject>Cell Proliferation - drug effects</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Cytochrome P-450 Enzyme System - physiology</subject><subject>Cytochrome P450 Family 4</subject><subject>Disease Models, Animal</subject><subject>Epithelial Cells - physiology</subject><subject>Hydroxyeicosatetraenoic Acids - antagonists & inhibitors</subject><subject>Hydroxyeicosatetraenoic Acids - physiology</subject><subject>Kidneys</subject><subject>Malformations of the urinary system</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Polycystic Kidney Diseases - etiology</subject><subject>Polycystic Kidney Diseases - metabolism</subject><subject>Polycystic Kidney Diseases - pathology</subject><issn>1046-6673</issn><issn>1533-3450</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1vFDEMhiMEoqVw5Yhygdss-c7MBalalhZRoIL2HHkzHhqUTZZkFmn_fVN11YJ8iGU_fm3HhLzmbMFNz99DTQvBmL0zy5-QY66l7KTS7GnzmTKdMVYekRe1_maMa2Htc3LEez0YLtQxuRasO19drehXHAPMWOllyTFMWGAOOdE80R-YINLVNsw3GENzlxhjpSHRyxz3fl_n4OmXMCbc04-hIlR8SZ5NECu-Orwn5PrT6mp53l18P_u8PL3ovOrV3HFrtZkGIUYhEXrtJ8G0WEvNve0HZe0awY7Qi8kOkvPGtYCGluUgRqXkCflwr7vdrTc4ekxzgei2JWyg7F2G4P7PpHDjfuW_TmjNtRFN4N1BoOQ_O6yz24Tq236QMO-qM4NhWgrZwMU96EuuteD00IQzd3cJd_rzm3u8RCt48-9oj_jh6xvw9gBA9RCnAsmH-sAJZrnWSstbZz2Qyw</recordid><startdate>20081001</startdate><enddate>20081001</enddate><creator>PARK, Frank</creator><creator>SWEENEY, William E</creator><creator>GUANGFU JIA</creator><creator>ROMAN, Richard J</creator><creator>AVNER, Ellis D</creator><general>Lippincott Williams & Wilkins</general><general>American Society of Nephrology</general><scope>IQODW</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20081001</creationdate><title>20-HETE Mediates Proliferation of Renal Epithelial Cells in Polycystic Kidney Disease</title><author>PARK, Frank ; SWEENEY, William E ; GUANGFU JIA ; ROMAN, Richard J ; AVNER, Ellis D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c484t-17756f922d23ea85cf2052b351c789477bea7da82f7931122dbea5a1c71a2d443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Amidines - pharmacology</topic><topic>Animals</topic><topic>Basic Research</topic><topic>Biological and medical sciences</topic><topic>Cell Culture Techniques</topic><topic>Cell Proliferation - drug effects</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Cytochrome P-450 Enzyme System - physiology</topic><topic>Cytochrome P450 Family 4</topic><topic>Disease Models, Animal</topic><topic>Epithelial Cells - physiology</topic><topic>Hydroxyeicosatetraenoic Acids - antagonists & inhibitors</topic><topic>Hydroxyeicosatetraenoic Acids - physiology</topic><topic>Kidneys</topic><topic>Malformations of the urinary system</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Polycystic Kidney Diseases - etiology</topic><topic>Polycystic Kidney Diseases - metabolism</topic><topic>Polycystic Kidney Diseases - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PARK, Frank</creatorcontrib><creatorcontrib>SWEENEY, William E</creatorcontrib><creatorcontrib>GUANGFU JIA</creatorcontrib><creatorcontrib>ROMAN, Richard J</creatorcontrib><creatorcontrib>AVNER, Ellis D</creatorcontrib><collection>Pascal-Francis</collection><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>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the American Society of Nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PARK, Frank</au><au>SWEENEY, William E</au><au>GUANGFU JIA</au><au>ROMAN, Richard J</au><au>AVNER, Ellis D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>20-HETE Mediates Proliferation of Renal Epithelial Cells in Polycystic Kidney Disease</atitle><jtitle>Journal of the American Society of Nephrology</jtitle><addtitle>J Am Soc Nephrol</addtitle><date>2008-10-01</date><risdate>2008</risdate><volume>19</volume><issue>10</issue><spage>1929</spage><epage>1939</epage><pages>1929-1939</pages><issn>1046-6673</issn><eissn>1533-3450</eissn><coden>JASNEU</coden><abstract>Polycystic kidney diseases are characterized by abnormal proliferation of renal epithelial cells. In this study, the role of 20-hydroxyeicosatetraenoic acid (20-HETE), an endogenous cytochrome P450 metabolite of arachidonic acid with mitogenic properties, was evaluated in cystic renal disease. Daily administration of HET-0016, an inhibitor of 20-HETE synthesis, significantly reduced kidney size by half in the BPK mouse model of autosomal recessive polycystic kidney disease. In addition, compared with untreated BPK mice, this treatment significantly reduced collecting tubule cystic indices and approximately doubled survival. For evaluation of the role of 20-HETE as a mediator of epithelial cell proliferation, principal cells isolated from cystic BPK and noncystic Balb/c mice were genetically modified using lentiviral vectors. Noncystic Balb/c cells overproducing Cyp4a12 exhibited a four- to five-fold increase in cell proliferation compared with control Balb/c cells, and this increase was completely abolished when 20-HETE synthesis was inhibited; therefore, this study suggests that 20-HETE mediates proliferation of epithelial cells in the formation of renal cysts.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>18596124</pmid><doi>10.1681/asn.2007070771</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amidines - pharmacology Animals Basic Research Biological and medical sciences Cell Culture Techniques Cell Proliferation - drug effects Cytochrome P-450 Enzyme System - metabolism Cytochrome P-450 Enzyme System - physiology Cytochrome P450 Family 4 Disease Models, Animal Epithelial Cells - physiology Hydroxyeicosatetraenoic Acids - antagonists & inhibitors Hydroxyeicosatetraenoic Acids - physiology Kidneys Malformations of the urinary system Medical sciences Mice Mice, Inbred BALB C Nephrology. Urinary tract diseases Polycystic Kidney Diseases - etiology Polycystic Kidney Diseases - metabolism Polycystic Kidney Diseases - pathology |
| title | 20-HETE Mediates Proliferation of Renal Epithelial Cells in Polycystic Kidney Disease |
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