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: 13.22). 07/1989; 83(6):2085-92. DOI: 10.1172/JCI114121
Source: PubMed


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; 50(2). DOI:10.1530/JME-12-0216 · 3.08 Impact Factor
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    • "In human utero-placental tissues the traditional vasoconstrictor components of the RAS are ubiquitous [11-16]. As to vasodilator peptides and receptors of the RAS, Broughton-Pipkin and her group have recently shown higher early expression of the receptor of Ang IV in the syncytiotrophoblast and extravillous trophoblast [12]; in addition, our laboratories have shown that Ang-(1–7) and ACE2 are expressed in multiple sites of the utero-placental interface [17,18]. "
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    ABSTRACT: Background In humans, trophoblast invasion, vascular remodeling and placental development are critical to determine the fate of pregnancy. Since guinea-pigs (GP) and humans share common pregnancy features including extensive trophoblast invasion, transformation of the uterine spiral arteries and a haemomonochorial placenta, the GP animal model was deemed suitable to extend our knowledge on the spatio-temporal immunoreactive expression of the vasodilator arpeptide of the renin-angiotensin system, angiotensin-(1–7) [Ang-(1–7)] and its main generating enzyme, angiotensin converting enzyme 2 (ACE2). Methods Utero-placental units were collected in days 15, 20, 40 and 60 of a 64–67 day long pregnancy in 25 Pirbright GP. Ang-(1–7) and ACE2 expression in utero-placental units were evaluated by immunohistochemistry. Results Ang-(1–7) and ACE2 were detected in the endothelium and syncytiotrophoblast of the labyrinthine placenta, interlobium, subplacenta, giant cells, syncytial sprouts, syncytial streamers, and myometrium throughout pregnancy. In late pregnancy, perivascular or intramural trophoblasts in spiral and mesometrial arteries expressed both factors. Immunoreactive Ang-(1–7) and ACE2 were present in decidua and in the vascular smooth muscle of spiral, myometrial and mesometrial arteries, which also express kallikrein (Kal), the bradykinin receptor 2 (B2R), vascular endothelial growth factor (VEGF) and its type 2 receptor (KDR), but no endothelial nitric oxide synthase (eNOS). In addition, the signal of Ang-(1–7) and ACE2 was especially remarkable in giant cells, which also show Kal, B2R. eNOS, VEGF and KDR. Conclusions The spatio-temporal expression of Ang-(1–7) and ACE2 in GP, similar to that of humans, supports a relevant evolutionary conserved function of Ang-(1–7) and ACE2 in decidualization, trophoblast invasion, vascular remodeling and placental flow regulation, as well as the validity of the GP model to understand the local adaptations of pregnancy. It also integrates Ang-(1–7) to the utero-placental vasodilatory network. However, its antiangiogenic effect may counterbalance the proangiogenic activity of some of the other vasodilator components.
    Reproductive Biology and Endocrinology 01/2013; 11(1):5. DOI:10.1186/1477-7827-11-5 · 2.23 Impact Factor
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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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