Article

Human decidua is a major source of renin

Department of Medicine, University of Southern California, School of Medicine, Los Angeles 90033.
Journal of Clinical Investigation (Impact Factor: 13.77). 07/1989; 83(6):2085-92. DOI: 10.1172/JCI114121
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ABSTRACT Plasma prorenin levels are elevated in normal pregnant women. Current evidence suggests renin production by tissues of the uteroplacental unit contribute to this elevation. The purpose of this investigation was to define the source of renin biosynthesis within the human uteroplacental unit and to characterize the renin produced. RNA extraction and Northern blot analysis consistently demonstrated renin mRNA expression in uterine lining both in the pregnant (decidua) and nonpregnant states (endometrium) and in fetal chorion laeve, which is inseparable from the decidua. In contrast, renin mRNA expression was not detected in basal plate and intertwin chorion (which is separate from decidua), amnion, myometrium, or placental villi. The total renin content in decidual homogenates was two- to threefold greater than in endometrial homogenates, and cultured human decidual cells produced significantly more total renin than cultured human endometrial cells, suggesting that pregnancy enhanced renin production by the cells lining the uterus. Immunoblot analysis and [3H]leucine incorporation identified 47,000-mol wt prorenin as the major form of renin produced by cultured human decidual cells. These studies indicate that maternal decidua is the major source of prorenin in the uteroplacental unit.

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    • "It has been confirmed that the components of RAS are not unique to the kidney but are synthesized in many tissues, among which one of the major local RAS during pregnancy is in the uteroplacental unit (placenta also named fetal origin and decidua named maternal origin) (Shah 2006). Since the first-time pro-renin, AGT, ACE, ANG II and ANG I, AT1R were identified in fetal placental tissues (Li et al. 1998), the expression of renin, AGT, ACE, and AT1R has been observed in the first trimester human deciduas (Shaw et al. 1989), and more recent studies via human third trimester decidual cells also have demonstrated the presence of AGT and renin (Li et al. 2000). Other studies of the decidual spiral arteries have indicated the expression of AGT, renin, ACE, and AT1R (Morgan et al. 1998a,b). "
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    ABSTRACT: The compensatory alterations in rennin-angiotensin-aldosterone System (RAAS) contribute to the salt-water-balance and sufficient placental perfusion for the subsequent well-being of the mother and fetus during normal pregnancy and is characterized by an increase in almost all of the components of RAAS. Preeclampsia, however, breaks homeostasis and leads to a disturbance of this delicate equilibrium in RAAS both for circulation and the uteroplacental unit. Despite being a major cause for maternal and neonatal morbidity and mortality, the pathogenesis of preeclampsia remains elusive, where RAAS has been long considered to be involved. Epidemiological studies have indicated that preeclampsia is a multifactorial disease with a strong familiar predisposition regardless of variations in ethnic, socioeconomic and geographic features. The heritable allelic variations, especially the genetic polymorphisms in RAAS, could be the foundation for the genetics of preeclampsia and hence are related to the development of preeclampsia. Furthermore, at a posttranscriptional level, microRNA (miRNA) can interacts with the targeted site within the 3'-untranslated region (3'-UTR) of RAAS gene, and thereby might participate in the regulation of RAAS and pathology of preeclampsia. In this review, we discuss the recent achievements of genetic polymorphisms, as well as the interactions between maternal and fetal genotypes, and miRNA posttranscriptional regulation associated with RAAS in preeclampsia, . The results are controversial but utterly inspiring and attractive in terms of potential prognostic significance. Although many studies suggest positive associations with genetic mutation and increased risk for preeclampsia, more meticulously designed larger-scale investigations are needed to avoid the interference from different variations.
    Journal of Molecular Endocrinology 01/2013; DOI:10.1530/JME-12-0216
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    • "Prorenin (45-47 kDa containing 406 amino acid residues), the pre-active form of renin, is predominantly synthesized by granular cells of the juxtaglomerular apparatus (JGA) in the terminal afferent arteriole (Schnermann & Briggs, 2008; Schweda et al., 2007) and principle cells of the collecting ducts (Prieto-Carrasquero et al., 2004; Rohrwasser et al., 1999; Kang et al., 2008). Prorenin is also synthesized in many other tissues like adrenal glands (Ganten et al., 1974, 1976; Ho and Vinson, 1998), zona glomerulosa (Doi et al., 1984; Deschepper, et al., 1986; Brecher et al., 1989), eye, Müller cells, mast cells (Krop et al., 2008), ovarian follicular fluid (Glorioso et al., 1986), and theca cells (Do et al., 1988), uterus (Derkx et al., 1987; Itskovitz et al., 1987), myometrium/decidual cells (Shaw et al., 1989), placenta (Lenz et al., 1991), chorionic cells, testis and leydig cells (Sealey et al., 1988). The submandibular gland in some mice strains produces a large amount of renin, which is a product of the Ren-2 renin gene distinct from the renal renin gene, Ren-1 (Cohen et al., 1972; Wilson et al., 1981; Holm et al., 1984) and this action is mediated by prorenin converting enzyme present in submandibular gland of the same mice strains (Kim et al., 1991). "
    Protein Interactions, 03/2012; , ISBN: 978-953-51-0244-1
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    • "Very high levels of prorenin-like activity are found in human amniotic fluid, decidua, chorion and placenta [1]. Although the decidua is the major site of prorenin production in intrauterine tissues [2], lower prorenin (REN) mRNA has been identified in late gestation placenta, amnion and chorion [3]. The (pro)renin receptor (ATPase H þ -transporting lysosomal accessory protein 2: ATP6AP2) has been described in placenta [4] and recently in other late gestation intrauterine and fetal tissues [3]. "
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    ABSTRACT: A prorenin-angiotensin system (RAS) could, via the (pro)renin receptor (ATP6AP2), have various effects in human intrauterine tissues, either directly by prorenin/ATP6AP2 cell signaling, or indirectly via angiotensin II and/or angiotensin 1-7. Here we describe RAS components in fetal membranes, decidua and placenta collected at elective cesarean section (non-laboring), after spontaneous delivery (after labor, n = 38), and in myometria (n = 16) from elective (non-laboring) or emergency cesarean (laboring) deliveries. Angiotensinogen (AGT), angiotensin-converting enzyme 1 and 2 (ACE; ACE2), angiotensin receptor 1 and 2 (AGTR1; AGTR2) and angiotensin 1-7 receptor (MAS1) mRNAs were measured by qRT-PCR and proteins were localized by immunohistochemistry. In myometrium, prorenin (REN), ATP6AP2, and downstream signaling proteins zinc finger and BTB domain-containing protein 16 (ZBTB16), transforming growth factor-β1 (TGFβ1) and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNAs were also measured. RAS mRNAs, except AGTR1 and AGTR2, were abundant in decidua and lowest in amnion compared to the other tissues. ACE, AGT and PTGS2 mRNAs were higher in laboring than non-laboring myometrium, suggesting that the myometrial RAS is involved in labor. Angiotensinogen and prorenin staining in amnion, chorion and decidua was pervasive despite their mRNAs being low in amnion and chorion. In placenta, prorenin, angiotensinogen and AGTR2 were present in syncytiotrophoblasts, ACE was in fetal endothelium, while ACE2 distribution was diffuse. AGTR1 and AGTR2 mRNAs and proteins were abundant. No differences were evident in the staining patterns with labor. These results are consistent with the hypothesis that fetal vascular ACE might contribute angiotensin II to the fetus, whilst syncytial ACE2 might hypothetically have a role in converting angiotensin II to angiotensin 1-7 in maternal blood.
    Placenta 03/2011; 32(3):214-21. DOI:10.1016/j.placenta.2010.12.006
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