Role of pro-IGF-II processing by proprotein convertase 4 in human placental development

Qiu, Qing; Basak, Ajoy; Mbikay, Majambu; Tsang, Benjamin K.; Gruslin, Andrée

doi:10.1073/pnas.0502357102

Cited by 99 publications

(93 citation statements)

References 41 publications

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“…Given the likelihood of compensatory evolution of other genes in these species, it would be difficult to ascertain the effect of these mutations on fetal growth in the fishes. In human fetuses, however, deficiency in posttranslational processing of the IGF2 prohormone and persistence of the large BCADE form leads to intrauterine growth retardation (23).…”

Section: Resultsmentioning

confidence: 99%

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Ancient and continuing Darwinian selection on insulin-like growth factor II in placental fishes

O’Neill

Lawton

Mateos

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Despite abundant examples of both adaptation at the level of phenotype and Darwinian selection at the level of genes, correlations between these two processes are notoriously difficult to identify. Positive Darwinian selection on genes is most easily discerned in cases of genetic conflict, when antagonistic evolutionary processes such as a Red Queen race drive the rate of nonsynonymous substitution above the neutral mutation rate. Genomic imprinting in mammals is thought to be the product of antagonistic evolution coincident with evolution of the placenta, but imprinted loci lack evidence of positive selection likely because of the ancient origin of viviparity in mammals. To determine whether genetic conflict is a general feature of adaptation to placental reproduction, we performed comparative evolutionary analyses of the insulin-like growth factor II (IGF2) gene in teleost fishes. Our analysis included several members of the order Cyprinodontiformes, in which livebearing and placentation have evolved several times independently. We found that IGF2 is subject to positive Darwinian selection coincident with the evolution of placentation in fishes, with particularly strong selection among lineages that have evolved placentation recently. Positive selection is also detected along ancient lineages of placental livebearing fishes, suggesting that selection on IGF2 function is ongoing in placental species. Our observations provide a rare example of natural selection acting in synchrony at the phenotypic and molecular level. These results also constitute the first direct evidence of parent-offspring conflict driving gene evolution.genomic imprinting ͉ parent-offspring conflict ͉ placentation ͉ positive selection ͉ sexual antagonism

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Section: Resultsmentioning

confidence: 99%

“…In all vertebrates, the IGF2 prepropeptide undergoes two essential proteolytic cleavages: one to remove the signal peptide and a second to remove the E domain to produce the mature hormone (Fig. 3A) (22,23).…”

Section: Resultsmentioning

confidence: 99%

Ancient and continuing Darwinian selection on insulin-like growth factor II in placental fishes

O’Neill

Lawton

Mateos

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…To date, seven PC isozymes have been identified: furin, PC1/3, PC2, PC4, PACE4, PC5/PC6, and PC7. Among them, it has been recently shown that PC4 is responsible for the physiological processing of IGF-II precursor in the placenta [4]; PC4 expressed in human placenta specifically cleaves the 156-residue pro-IGF-II at Arg-104 and Arg-68 to generate a HMW form and a mature 67-residue IGF-II [4,12].…”

Section: Discussionmentioning

confidence: 99%

“…However, it has been recently shown that prohormone convertase (PC) 4 is involved in the processing of IGF-II precursor in human placental tissue where mature IGF-II is produced [4]. Thus PC4 may be a candidate enzyme responsible for the physiological processing of IGF-II precursor.…”

mentioning

confidence: 99%

Defective Expression of Prohormone Convertase 4 and Enhanced Expression of Insulin-like Growth Factor II by Pleural Solitary Fibrous Tumor Causing Hypoglycemia

et al. 2008

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Abstract.A 75-year-old man was admitted to our hospital because of unconsciousness. His plasma glucose was very low, but his serum levels of insulin and IGF-I were also low. He was found to have a giant solitary pleural tumor, which was completely resected, after which his hypoglycemia ameliorated postoperatively. Histologically, the tumor was consistent with the pathological diagnosis of a solitary fibrous tumor derived from the pleura. Immunohistochemical study revealed positive immunostaining for IGF-II in tumor cells. The presence of high molecular weight (HMW) form of IGF-II in the tumor tissue and patient's serum was confirmed by Western blot analysis. Steady-state mRNA levels of IGF-II and prohormone convertases (PC) 4, a potential protease responsible for IGF-II processing, as determined by RT-PCR were about 14-fold greater and 5-fold less in the tumor tissue than those in normal placental tissue, respectively. Therefore, it is suggested that biologically active, unprocessed HMW form of IGF-II generated from the impaired processing of IGF-II precursor by the defective PC4 expression in the tumor was responsible for the non-islet cell tumor hypoglycemia (NICTH) in the present case.

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“…Conversely, underweight women give birth to proportionately greater number of small for gestational age (SGA), and significantly fewer LGA neonates [114]. In growth restricted fetuses for example, IGF cord serum concentrations remain low compared to appropriately sized neonates [115,116]. Additional support for the growth-promoting role of IGF-I comes from transgenic mice with a homozygous defect of the igf1 gene (IGF1 knockout) who display significant embryonic and postnatal growth retardation [117,118].…”

Section: Insulin-like Growth Factors and Fetal Growthmentioning

confidence: 99%

An examination of maternal contributors and potential modifiers of fetal growth in pregnancy

Ferraro

2013

Appl. Physiol. Nutr. Metab.

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A greater understanding of critical periods of body weight regulation, including pregnancy, may aid in efforts to optimize weight management strategies for the mother and her baby.The gestational period has been implicated to play, in the child, a vital role in the developmental origins of obesity and other cardiometabolic diseases later in life. Therefore, we initially examined existing literature on the role of maternal obesity and its link to pediatric obesity and documented the known underlying physiological mechanisms responsible for this relationship while suggesting potential intervention targets that may improve maternal-fetal outcomes. In a second paper, we aimed to quantify maternal predictors of large for gestational age (LGA) neonates in the Ottawa and Kingston (OaK) birth cohort with specific hypotheses verifying the independent contribution of maternal prepregnancy body mass index (BMI) and excessive gestational weight gain (GWG) to fetal overgrowth. This paper also highlights the clinical utility of the revised 2009 Institute of Medicine GWG guidelines and discusses the potential role of physiological factors underlying the observed associations between BMI, excessive GWG and LGA neonates. As a follow-up to our population-level analysis (i.e., OAK cohort), papers three and four highlight how the insulin-like growth factor (IGF) axis, a vital regulator of growth and development, may be compromised at the molecular level in cases of maternal obesity (paper 3) and excessive GWG (paper 4). In paper 3 we show that maternal obesity is associated with attenuated expression of IGF binding protein-4 (IGFBP4) in umbilical cord blood and discuss how this may preferentially promote fetal adipogenesis. The effects of excessive GWG on IGF axis protein expression are addressed in paper four where we show iii that excessive weight gain during pregnancy is associated with increased expression of IGFBP3 in maternal circulation in normoglycemic term pregnancies. In this paper we discuss the potential inhibitory role of IGFBP3 on adipogenesis and how it relates to glucose intolerance during pregnancy. Recognizing that both obesity and excessive GWG can alter physiological processes in mother and her baby, appropriate evidence-based interventions are warranted to best optimize outcomes. In paper five, we discuss the results of a study which sought to assess patient information channels and knowledge of nutrition and physical activity during pregnancy with the intent that these findings be applied to best design efficacious strategies that cater to the needs of our target group of pregnant women. In our analysis we show that the majority of pregnant women studied would be willing to participate in a lifestyle intervention for their own personal health and that of their child. Of great interest was the observation that most women were not informed of the importance of pregnancy-specific energy intake, or made aware of their own healthy GWG targets. Additionally, many of the respondents reported receiving no info...

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Role of pro-IGF-II processing by proprotein convertase 4 in human placental development

Cited by 99 publications

References 41 publications

Ancient and continuing Darwinian selection on insulin-like growth factor II in placental fishes

Ancient and continuing Darwinian selection on insulin-like growth factor II in placental fishes

Defective Expression of Prohormone Convertase 4 and Enhanced Expression of Insulin-like Growth Factor II by Pleural Solitary Fibrous Tumor Causing Hypoglycemia

An examination of maternal contributors and potential modifiers of fetal growth in pregnancy

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