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Reduced expression of 11β-hydroxysteroid dehydrogenase type 2 in preeclamptic placentas is associated with decreased PPARγ but increased PPARα expression.
Endocrinology. 2014 Jan; 155(1):299-309.E

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.

Authors+Show Affiliations

Department of Physiology (P.H., Z.C., X.N.) and Department of Obstetrics and Gynecology (Q.S., Y.L., H.G.), Changhai Hospital, Second Military Medical University, Shanghai 200433, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24169559

Citation

He, Ping, et al. "Reduced Expression of 11β-hydroxysteroid Dehydrogenase Type 2 in Preeclamptic Placentas Is Associated With Decreased PPARγ but Increased PPARα Expression." Endocrinology, vol. 155, no. 1, 2014, pp. 299-309.
He P, Chen Z, Sun Q, et al. Reduced expression of 11β-hydroxysteroid dehydrogenase type 2 in preeclamptic placentas is associated with decreased PPARγ but increased PPARα expression. Endocrinology. 2014;155(1):299-309.
He, P., Chen, Z., Sun, Q., Li, Y., Gu, H., & Ni, X. (2014). Reduced expression of 11β-hydroxysteroid dehydrogenase type 2 in preeclamptic placentas is associated with decreased PPARγ but increased PPARα expression. Endocrinology, 155(1), 299-309. https://doi.org/10.1210/en.2013-1350
He P, et al. Reduced Expression of 11β-hydroxysteroid Dehydrogenase Type 2 in Preeclamptic Placentas Is Associated With Decreased PPARγ but Increased PPARα Expression. Endocrinology. 2014;155(1):299-309. PubMed PMID: 24169559.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced expression of 11β-hydroxysteroid dehydrogenase type 2 in preeclamptic placentas is associated with decreased PPARγ but increased PPARα expression. AU - He,Ping, AU - Chen,Zhaoguang, AU - Sun,Qianqian, AU - Li,Yuan, AU - Gu,Hang, AU - Ni,Xin, Y1 - 2013/12/04/ PY - 2013/10/31/entrez PY - 2013/10/31/pubmed PY - 2014/2/25/medline SP - 299 EP - 309 JF - Endocrinology JO - Endocrinology VL - 155 IS - 1 N2 - 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. SN - 1945-7170 UR - https://www.unboundmedicine.com/medline/citation/24169559/Reduced_expression_of_11β_hydroxysteroid_dehydrogenase_type_2_in_preeclamptic_placentas_is_associated_with_decreased_PPARγ_but_increased_PPARα_expression_ DB - PRIME DP - Unbound Medicine ER -