Reduced Expression of 11β-Hydroxysteroid Dehydrogenase Type 2 in Preeclamptic Placentas Is Associated With Decreased PPARγ but Increased PPARα Expression
Placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is reduced in pregnancies complicated with preeclampsia (PE). Peroxisome proliferator-activated receptors β/δ (PPARβ/δ) have been shown to suppress 11β-HSD2 expression in human placental cells. Our objectives were to investigate whether th...
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description | Placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is reduced in pregnancies complicated with preeclampsia (PE). Peroxisome proliferator-activated receptors β/δ (PPARβ/δ) have been shown to suppress 11β-HSD2 expression in human placental cells. Our objectives were to investigate whether the reduced 11β-HSD2 expression is associated with the changes in PPARs in PE placentas, and whether PPARα and PPARγ affect 11β-HSD2 expression in placental cells. PPARα and PPARβ/δ mRNA and protein expression was increased, whereas PPARγ mRNA and protein expression was decreased in PE placentas. 11β-HSD2 protein expression was inversely correlated with PPARβ/δ in normal placentas but correlated positively with PPARγ and inversely to PPARα in PE placentas. In cultured placental cells, PPARα agonist inhibited, whereas PPARγ agonist stimulated, 11β-HSD2 mRNA and protein expression and activity in a dose-dependent manner. Knockdown of retinoid X nuclear receptor α (RXRα) resulted in a loss of PPARγ effect but not PPARα effect on11β-HSD2. The PPARα effect remained, but the PPARγ effect was lost in the presence of the translational inhibitor cycloheximide. PPARγ agonist dose-dependently stimulated specificity protein 1 (Sp-1) protein expression. Inhibition or knockdown of Sp-1 resulted in a loss of the effects of PPARα and PPARγ. The Sp-1 protein level was not correlated with 11β-HSD2 and PPARs in normal placentas, whereas Sp-1 expression was correlated with 11β-HSD2, PPARγ, and PPARβ/δ in PE placentas. Our data indicate that 11β-HSD2 expression can be modulated by PPARα and PPARγ in placental trophoblasts through Sp-1. Decreased 11β-HSD2 expression in PE placenta might be associated with decreased PPARγ but increased PPARα expression. |
doi_str_mv | 10.1210/en.2013-1350 |
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Peroxisome proliferator-activated receptors β/δ (PPARβ/δ) have been shown to suppress 11β-HSD2 expression in human placental cells. Our objectives were to investigate whether the reduced 11β-HSD2 expression is associated with the changes in PPARs in PE placentas, and whether PPARα and PPARγ affect 11β-HSD2 expression in placental cells. PPARα and PPARβ/δ mRNA and protein expression was increased, whereas PPARγ mRNA and protein expression was decreased in PE placentas. 11β-HSD2 protein expression was inversely correlated with PPARβ/δ in normal placentas but correlated positively with PPARγ and inversely to PPARα in PE placentas. In cultured placental cells, PPARα agonist inhibited, whereas PPARγ agonist stimulated, 11β-HSD2 mRNA and protein expression and activity in a dose-dependent manner. Knockdown of retinoid X nuclear receptor α (RXRα) resulted in a loss of PPARγ effect but not PPARα effect on11β-HSD2. The PPARα effect remained, but the PPARγ effect was lost in the presence of the translational inhibitor cycloheximide. PPARγ agonist dose-dependently stimulated specificity protein 1 (Sp-1) protein expression. Inhibition or knockdown of Sp-1 resulted in a loss of the effects of PPARα and PPARγ. The Sp-1 protein level was not correlated with 11β-HSD2 and PPARs in normal placentas, whereas Sp-1 expression was correlated with 11β-HSD2, PPARγ, and PPARβ/δ in PE placentas. Our data indicate that 11β-HSD2 expression can be modulated by PPARα and PPARγ in placental trophoblasts through Sp-1. Decreased 11β-HSD2 expression in PE placenta might be associated with decreased PPARγ but increased PPARα expression.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2013-1350</identifier><identifier>PMID: 24169559</identifier><language>eng</language><publisher>United States: Endocrine Society</publisher><subject>11-beta-Hydroxysteroid Dehydrogenase Type 2 - metabolism ; 11β-Hydroxysteroid dehydrogenase ; Adult ; Agonists ; Cells, Cultured ; Correlation ; Cycloheximide ; Dehydrogenase ; Dehydrogenases ; Female ; Gene expression ; Gene Expression Regulation, Enzymologic ; Humans ; Hydroxysteroids ; mRNA ; Peroxisome proliferator-activated receptors ; Placenta ; Placenta - enzymology ; PPAR alpha - metabolism ; PPAR gamma - metabolism ; Pre-eclampsia ; Pre-Eclampsia - enzymology ; Pregnancy ; Pregnancy complications ; Promoter Regions, Genetic ; Protein expression ; Proteins ; Real-Time Polymerase Chain Reaction ; Receptors ; RNA Interference ; Signal Transduction ; Sp1 Transcription Factor - metabolism ; Trophoblasts ; Trophoblasts - enzymology</subject><ispartof>Endocrinology (Philadelphia), 2014-01, Vol.155 (1), p.299-309</ispartof><rights>Copyright © 2014 by The Endocrine Society</rights><rights>Copyright © 2014 by The Endocrine Society 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-1b7033d158499c281aa0748606bf0b4acb57aeee342fe434860b7bc2c49352fc3</citedby><cites>FETCH-LOGICAL-c433t-1b7033d158499c281aa0748606bf0b4acb57aeee342fe434860b7bc2c49352fc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24169559$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>He, Ping</creatorcontrib><creatorcontrib>Chen, Zhaoguang</creatorcontrib><creatorcontrib>Sun, Qianqian</creatorcontrib><creatorcontrib>Li, Yuan</creatorcontrib><creatorcontrib>Gu, Hang</creatorcontrib><creatorcontrib>Ni, Xin</creatorcontrib><title>Reduced Expression of 11β-Hydroxysteroid Dehydrogenase Type 2 in Preeclamptic Placentas Is Associated With Decreased PPARγ but Increased PPARα Expression</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is reduced in pregnancies complicated with preeclampsia (PE). Peroxisome proliferator-activated receptors β/δ (PPARβ/δ) have been shown to suppress 11β-HSD2 expression in human placental cells. Our objectives were to investigate whether the reduced 11β-HSD2 expression is associated with the changes in PPARs in PE placentas, and whether PPARα and PPARγ affect 11β-HSD2 expression in placental cells. PPARα and PPARβ/δ mRNA and protein expression was increased, whereas PPARγ mRNA and protein expression was decreased in PE placentas. 11β-HSD2 protein expression was inversely correlated with PPARβ/δ in normal placentas but correlated positively with PPARγ and inversely to PPARα in PE placentas. In cultured placental cells, PPARα agonist inhibited, whereas PPARγ agonist stimulated, 11β-HSD2 mRNA and protein expression and activity in a dose-dependent manner. Knockdown of retinoid X nuclear receptor α (RXRα) resulted in a loss of PPARγ effect but not PPARα effect on11β-HSD2. The PPARα effect remained, but the PPARγ effect was lost in the presence of the translational inhibitor cycloheximide. PPARγ agonist dose-dependently stimulated specificity protein 1 (Sp-1) protein expression. Inhibition or knockdown of Sp-1 resulted in a loss of the effects of PPARα and PPARγ. The Sp-1 protein level was not correlated with 11β-HSD2 and PPARs in normal placentas, whereas Sp-1 expression was correlated with 11β-HSD2, PPARγ, and PPARβ/δ in PE placentas. Our data indicate that 11β-HSD2 expression can be modulated by PPARα and PPARγ in placental trophoblasts through Sp-1. Decreased 11β-HSD2 expression in PE placenta might be associated with decreased PPARγ but increased PPARα expression.</description><subject>11-beta-Hydroxysteroid Dehydrogenase Type 2 - metabolism</subject><subject>11β-Hydroxysteroid dehydrogenase</subject><subject>Adult</subject><subject>Agonists</subject><subject>Cells, Cultured</subject><subject>Correlation</subject><subject>Cycloheximide</subject><subject>Dehydrogenase</subject><subject>Dehydrogenases</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Humans</subject><subject>Hydroxysteroids</subject><subject>mRNA</subject><subject>Peroxisome proliferator-activated receptors</subject><subject>Placenta</subject><subject>Placenta - enzymology</subject><subject>PPAR alpha - metabolism</subject><subject>PPAR gamma - metabolism</subject><subject>Pre-eclampsia</subject><subject>Pre-Eclampsia - enzymology</subject><subject>Pregnancy</subject><subject>Pregnancy complications</subject><subject>Promoter Regions, Genetic</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors</subject><subject>RNA Interference</subject><subject>Signal Transduction</subject><subject>Sp1 Transcription Factor - metabolism</subject><subject>Trophoblasts</subject><subject>Trophoblasts - enzymology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1O3DAYRa2qqAzQXdeVpS7KgoD_Mk6WI0phJKSOEKhLy3G-FKOMndqJxLwLL0H7HjxTHWZKfwQry5-Pj698EXpHySFllByBO2SE8ozynLxCE1qKPJNUktdoQsa5ZExuo50Yb9JWCMHfoG0m6LTM83KC7i6gHgzU-OS2CxCj9Q77BlP68CM7W9XB365iD8HbGn-C63HwDZyOgC9XHWCGrcOLAGBavex6a_Ci1QZcryOeRzyL0Rur-6T_avvrZDAB0uUaLxazi4efuBp6PHf_DO__SrKHthrdRni7WXfR1eeTy-Oz7PzL6fx4dp4ZwXmf0UoSzmuaF6IsDSuo1kSKYkqmVUMqoU2VSw0AXLAGBB9PKlkZZkTJc9YYvov2194u-O8DxF4tbTTQttqBH6KioiSySG-UCf3wH3rjh-BSOsUpJ1NWEJEn6mBNmeBjDNCoLtilDitFiRpbU-DU2JoaW0v4-410qJZQP8G_a0rAxzXgh-4lVbZR8TUJrvYmWAePn_kn5bMBfgH0XLGh</recordid><startdate>201401</startdate><enddate>201401</enddate><creator>He, Ping</creator><creator>Chen, Zhaoguang</creator><creator>Sun, Qianqian</creator><creator>Li, Yuan</creator><creator>Gu, Hang</creator><creator>Ni, Xin</creator><general>Endocrine Society</general><general>Oxford University Press</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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201401</creationdate><title>Reduced Expression of 11β-Hydroxysteroid Dehydrogenase Type 2 in Preeclamptic Placentas Is Associated With Decreased PPARγ but Increased PPARα Expression</title><author>He, Ping ; Chen, Zhaoguang ; Sun, Qianqian ; Li, Yuan ; Gu, Hang ; Ni, Xin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-1b7033d158499c281aa0748606bf0b4acb57aeee342fe434860b7bc2c49352fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>11-beta-Hydroxysteroid Dehydrogenase Type 2 - metabolism</topic><topic>11β-Hydroxysteroid dehydrogenase</topic><topic>Adult</topic><topic>Agonists</topic><topic>Cells, Cultured</topic><topic>Correlation</topic><topic>Cycloheximide</topic><topic>Dehydrogenase</topic><topic>Dehydrogenases</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Humans</topic><topic>Hydroxysteroids</topic><topic>mRNA</topic><topic>Peroxisome proliferator-activated receptors</topic><topic>Placenta</topic><topic>Placenta - enzymology</topic><topic>PPAR alpha - metabolism</topic><topic>PPAR gamma - metabolism</topic><topic>Pre-eclampsia</topic><topic>Pre-Eclampsia - enzymology</topic><topic>Pregnancy</topic><topic>Pregnancy complications</topic><topic>Promoter Regions, Genetic</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptors</topic><topic>RNA Interference</topic><topic>Signal Transduction</topic><topic>Sp1 Transcription Factor - metabolism</topic><topic>Trophoblasts</topic><topic>Trophoblasts - enzymology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, Ping</creatorcontrib><creatorcontrib>Chen, Zhaoguang</creatorcontrib><creatorcontrib>Sun, Qianqian</creatorcontrib><creatorcontrib>Li, Yuan</creatorcontrib><creatorcontrib>Gu, Hang</creatorcontrib><creatorcontrib>Ni, Xin</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>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology 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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>He, Ping</au><au>Chen, Zhaoguang</au><au>Sun, Qianqian</au><au>Li, Yuan</au><au>Gu, Hang</au><au>Ni, Xin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduced Expression of 11β-Hydroxysteroid Dehydrogenase Type 2 in Preeclamptic Placentas Is Associated With Decreased PPARγ but Increased PPARα Expression</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2014-01</date><risdate>2014</risdate><volume>155</volume><issue>1</issue><spage>299</spage><epage>309</epage><pages>299-309</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><abstract>Placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is reduced in pregnancies complicated with preeclampsia (PE). Peroxisome proliferator-activated receptors β/δ (PPARβ/δ) have been shown to suppress 11β-HSD2 expression in human placental cells. Our objectives were to investigate whether the reduced 11β-HSD2 expression is associated with the changes in PPARs in PE placentas, and whether PPARα and PPARγ affect 11β-HSD2 expression in placental cells. PPARα and PPARβ/δ mRNA and protein expression was increased, whereas PPARγ mRNA and protein expression was decreased in PE placentas. 11β-HSD2 protein expression was inversely correlated with PPARβ/δ in normal placentas but correlated positively with PPARγ and inversely to PPARα in PE placentas. In cultured placental cells, PPARα agonist inhibited, whereas PPARγ agonist stimulated, 11β-HSD2 mRNA and protein expression and activity in a dose-dependent manner. Knockdown of retinoid X nuclear receptor α (RXRα) resulted in a loss of PPARγ effect but not PPARα effect on11β-HSD2. The PPARα effect remained, but the PPARγ effect was lost in the presence of the translational inhibitor cycloheximide. PPARγ agonist dose-dependently stimulated specificity protein 1 (Sp-1) protein expression. Inhibition or knockdown of Sp-1 resulted in a loss of the effects of PPARα and PPARγ. The Sp-1 protein level was not correlated with 11β-HSD2 and PPARs in normal placentas, whereas Sp-1 expression was correlated with 11β-HSD2, PPARγ, and PPARβ/δ in PE placentas. Our data indicate that 11β-HSD2 expression can be modulated by PPARα and PPARγ in placental trophoblasts through Sp-1. Decreased 11β-HSD2 expression in PE placenta might be associated with decreased PPARγ but increased PPARα expression.</abstract><cop>United States</cop><pub>Endocrine Society</pub><pmid>24169559</pmid><doi>10.1210/en.2013-1350</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Journals@Ovid Complete |
subjects | 11-beta-Hydroxysteroid Dehydrogenase Type 2 - metabolism 11β-Hydroxysteroid dehydrogenase Adult Agonists Cells, Cultured Correlation Cycloheximide Dehydrogenase Dehydrogenases Female Gene expression Gene Expression Regulation, Enzymologic Humans Hydroxysteroids mRNA Peroxisome proliferator-activated receptors Placenta Placenta - enzymology PPAR alpha - metabolism PPAR gamma - metabolism Pre-eclampsia Pre-Eclampsia - enzymology Pregnancy Pregnancy complications Promoter Regions, Genetic Protein expression Proteins Real-Time Polymerase Chain Reaction Receptors RNA Interference Signal Transduction Sp1 Transcription Factor - metabolism Trophoblasts Trophoblasts - enzymology |
title | Reduced Expression of 11β-Hydroxysteroid Dehydrogenase Type 2 in Preeclamptic Placentas Is Associated With Decreased PPARγ but Increased PPARα Expression |
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