The Characterization of Pregnancy Associated Plasma Protein-E and the Identification of an Alternative Splice Variant

Page, Nigel M.; Butlin, David; Lomthaisong, Khomsorn; Lowry, P. J.

doi:10.1053/plac.2001.0709

Cited by 19 publications

(22 citation statements)

References 24 publications

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“…The estimated size of PAPPA2 was w250 kDa in both mouse and human (Figs 2 and 3), as found by Nishizawa et al (2008). In humans there was also a band of w130 kDa, which is close to the expected size of a splice variant of PAPPA2 (Page et al 2001). …”

Section: Western Blottingsupporting

confidence: 78%

“…Previously, Pappa2 expression was found to be higher in stomach than in a variety of other adult tissues, including brain, kidney, heart, lung, testis, pancreas, and prostate gland (Christians et al 2006). In humans, PAPPA2 has also been expressed much more strongly in placenta than in other adult tissues (Farr et al 2000, Page et al 2001. In contrast, while PAPPA is highly expressed in human placenta , Pappa expression in the murine placenta is not particularly high compared to other tissues (Qin et al 2002, Soe et al 2002.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, another protease similar to PAPPA has been identified (Farr et al 2000, Overgaard et al 2001, Page et al 2001 and designated as PAPPA2 (earlier names included PAPP-E and Plac3). Like PAPPA, PAPPA2 is abundantly expressed in the human placenta (Farr et al 2000, Page et al 2001, and also cleaves an IGFBP (Overgaard et al 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Like PAPPA, PAPPA2 is abundantly expressed in the human placenta (Farr et al 2000, Page et al 2001, and also cleaves an IGFBP (Overgaard et al 2001). Unlike PAPPA, which proteolyses both IGFBP4 and IGFBP5 (Boldt et al 2004), PAPPA2 cleaves IGFBP5 and may also show lower proteolytic activity against IGFBP3 (Overgaard et al 2001).…”

Section: Introductionmentioning

confidence: 99%

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Expression of pregnancy-associated plasma protein A2 during pregnancy in human and mouse

Wang¹,

Qiu²,

Haider³

et al. 2009

Journal of Endocrinology

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Pregnancy-associated plasma protein-A and -A2 (PAPPA and PAPPA2) are proteases that cleave IGF binding proteins (IGFBPs) and thereby increase the bioavailability of growth factors. PAPPA has long been recognized as a marker of fetal genetic disorders and adverse pregnancy outcomes. In contrast, although PAPPA2 is also highly expressed in human placenta, its physiological importance is not clear. To establish whether mice will be a useful model for the study of PAPPA2, we compared the patterns of expression of PAPPA2 in the placentae of mouse and human. We show, for the first time, that Pappa2 is highly expressed in mouse placenta, as is the case in humans. Specifically, it is expressed at the interface of the maternal and fetal layers of the mouse placenta at all gestational stages studied (10 . [5][6][7][8][9][10][11][12][13][14][15][16] . 5 days post coitum).Similarly, PAPPA2 is expressed in the syncytiotrophoblast layer of human placental villi and is also detected in some invasive extravillous trophoblasts in the first trimester. These results are consistent with a model whereby PAPPA2 cleaves IGFBPs produced in the maternal decidua to promote fetoplacental growth, and indicate that this protein may play analogous roles in human and mouse placenta. PAPPA2 protein is detectable in the circulation of pregnant mice and humans during the first trimester and at term, raising the possibility that PAPPA2 may be a useful biomarker of placental dysfunction. Pappa2 expression also shows specific localization within the mouse embryo and therefore may play roles in fetal development, independent of its action in the placenta.

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Section: Western Blottingsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expression of pregnancy-associated plasma protein A2 during pregnancy in human and mouse

Wang¹,

Qiu²,

Haider³

et al. 2009

Journal of Endocrinology

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“…Two proteases, PAPP-A and PAPP-A2 (Fig. 1), belong to the metzincin superfamily of pappalysins and to the class of Zn 2+ -dependent metalloproteases described [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

PAPP-A2 nowy regulator procesu wzrastania

Banaszak-Ziemska

Niedziela

2017

Endokrynologia Polska

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Short stature is the main problem that paediatric endocrinologists have to grapple with. Endocrine disorders account for only 5% of patients with short stature, but this is still one of the most common causes of reports to the endocrine clinic and hospitalisation in the endocrine department. A properly functioning growth hormone/insulin-like growth factor 1 (GH/IGF1) axis is one of the most important factors in proper growth. A lot of genetic defects in this axis lead to syndromes marked by impaired growth, like Laron syndrome, mutations in the STAT5B, insulin-like growth factor 1 (IGF1), and insulin-like growth factor 1 receptor (IGF1R) and mutations in the acid labile subunit (ALS). Two proteases important for the proper functioning of the GH/IGF1 axis: pregnancy-associated plasma protein-A (PAPP-A) and pregnancy-associated plasma protein-A2 (PAPP-A2), have been described. The first description of the new syndrome of growth failure associated with mutation in the PAPP-A2 gene was given by Andrew Dauber et al. This review evaluates the current data concerning PAPP-A2 function, and particularly the effect of PAPP-A2 mutation on growth. (Endokrynol Pol 2017; 68 (6): 682-687)

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Altered levels of insulin‐like growth factor binding protein proteases in preeclampsia and intrauterine growth restriction

Christians

Gruslin

2010

Prenatal Diagnosis

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Intrauterine growth restriction (IUGR) and preeclampsia (PE) are leading causes of perinatal and maternal morbidity and mortality. Many studies have found association between low levels of insulin-like growth factor binding protein (IGFBP) proteases in the first trimester maternal circulation and the risk of subsequent development of PE and/or IUGR. These results are generally interpreted to reflect decreased production of the proteases by the placenta, leading to reduced proteolysis of IGFBPs and lower free levels of insulin-like growth factor (IGF), resulting in diminished feto-placental development. However, the association between low circulating levels of placental proteins early in pregnancy and the subsequent development of IUGR and/or PE could be due to low exchange in the placenta and not due to reduced production. In contrast, late in pregnancy, the circulating levels of these proteins and their expression in the placenta are often elevated in PE, which may reflect upregulation to compensate for abnormal placental development, that is an adaptive mechanism to increase IGFBP proteolysis, increase local IGF levels and promote feto-placental growth. Further research into the biological mechanisms underlying these associations will aid the identification of high-risk pregnancies and the development of therapeutic targets for diseases for which there are presently no preventative measures.

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The Characterization of Pregnancy Associated Plasma Protein-E and the Identification of an Alternative Splice Variant

Cited by 19 publications

References 24 publications

Expression of pregnancy-associated plasma protein A2 during pregnancy in human and mouse

Expression of pregnancy-associated plasma protein A2 during pregnancy in human and mouse

PAPP-A2 nowy regulator procesu wzrastania

Altered levels of insulin‐like growth factor binding protein proteases in preeclampsia and intrauterine growth restriction

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