Klotho Gene and Protein in Human Placentas According to Birth Weight and Gestational Age
Introduction: Fetal growth restriction may be the consequence of maternal, fetal, or placental factors. The insulin-like growth factors (IGFs) are major determinants of fetal growth, and are expressed in the mother, fetus and placenta in most species. Previously we reported higher placental protein...
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| Format: | Article |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2018.00797/full |
| _version_ | 1811223446419406848 |
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| author | Germán Iñiguez Pedro Gallardo Juan Jose Castro Rene Gonzalez Mirna Garcia Elena Kakarieka Sebastian San Martin Maria Cecilia Johnson Verónica Mericq Fernando Cassorla |
| author_facet | Germán Iñiguez Pedro Gallardo Juan Jose Castro Rene Gonzalez Mirna Garcia Elena Kakarieka Sebastian San Martin Maria Cecilia Johnson Verónica Mericq Fernando Cassorla |
| author_sort | Germán Iñiguez |
| collection | DOAJ |
| description | Introduction: Fetal growth restriction may be the consequence of maternal, fetal, or placental factors. The insulin-like growth factors (IGFs) are major determinants of fetal growth, and are expressed in the mother, fetus and placenta in most species. Previously we reported higher placental protein content of IGF-I, IGF-IR, and AKT in small (SGA) compared with those from appropriate for gestational age (AGA) placentas. The protein Klotho, has been reported in placenta and may regulate IGF-I activity. In this study we determined Klotho gene expression and protein immunostaining in term (T-SGA y T-AGA) and preterm (PT-SGA y PT-AGA) human placentas. In addition, we assessed the effect of Klotho on the IGF-IR and AKT activation induced by IGF-I.Methods: Placentas (n = 1 17) from 32 T-SGA (birth weight (BW) = −1.74 ± 0.08 SDS), 37 T-AGA (BW = 0.12 ± 0.12 SDS), 20 PT-SGA (BW = −2.08 ± 0.14 SDS), and 28 PT-AGA (BW = −0.43 ± 0.13 SDS) newborns were collected. mRNA expression by RT-PCR in the chorionic (CP) and basal (BP) plates of the placentas, and the presence of Klotho was evaluated by immunohistochemistry (integral optical density, IOD). In addition, we developed placental explants that were incubated with IGF-I in the presence or absence of Klotho.Results: We found a lower mRNA expression and protein immunoreactivity of Klotho in the CP of SGA (term and preterm) compared with AGA placentas. We also observed a significant reduction in IGF-IR tyrosine activation induced by IGF-I 10 nM when preincubated with 2.0 nM of Klotho (2.4 ± 0.5 arbitrary units vs. 1.3 ± 0.3 AU), and similar results we observed on AKT and ERK42/44 activation.Conclusion: We describe for the first time that Klotho mRNA and protein varies according to fetal growth and gestational age. In addition, Klotho appears to down-regulate the activation induced by IGF-I on IGF-IR and AKT, suggesting that Klotho may be regulating IGF-I activity in human placentas according to intrauterine fetal growth. |
| first_indexed | 2024-04-12T08:33:07Z |
| format | Article |
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| language | English |
| last_indexed | 2024-04-12T08:33:07Z |
| publishDate | 2019-01-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-98c55c2489534fbd80149c5ca925576c2022-12-22T03:40:06ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-01-01910.3389/fendo.2018.00797415689Klotho Gene and Protein in Human Placentas According to Birth Weight and Gestational AgeGermán Iñiguez0Pedro Gallardo1Juan Jose Castro2Rene Gonzalez3Mirna Garcia4Elena Kakarieka5Sebastian San Martin6Maria Cecilia Johnson7Verónica Mericq8Fernando Cassorla9School of Medicine, Maternal and Child Research Institute (IDIMI), University of Chile, Santiago, ChileSchool of Medicine, Maternal and Child Research Institute (IDIMI), University of Chile, Santiago, ChileSchool of Medicine, Maternal and Child Research Institute (IDIMI), University of Chile, Santiago, ChileBiomedical Research Centre, School of Medicine, University of Valparaíso, Valparaíso, ChileNeonatology Unit, San Borja Arriarán Clinical Hospital, Santiago, ChilePathology Unit, San Borja Arriarán Clinical Hospital, Santiago, ChileBiomedical Research Centre, School of Medicine, University of Valparaíso, Valparaíso, ChileSchool of Medicine, Maternal and Child Research Institute (IDIMI), University of Chile, Santiago, ChileSchool of Medicine, Maternal and Child Research Institute (IDIMI), University of Chile, Santiago, ChileSchool of Medicine, Maternal and Child Research Institute (IDIMI), University of Chile, Santiago, ChileIntroduction: Fetal growth restriction may be the consequence of maternal, fetal, or placental factors. The insulin-like growth factors (IGFs) are major determinants of fetal growth, and are expressed in the mother, fetus and placenta in most species. Previously we reported higher placental protein content of IGF-I, IGF-IR, and AKT in small (SGA) compared with those from appropriate for gestational age (AGA) placentas. The protein Klotho, has been reported in placenta and may regulate IGF-I activity. In this study we determined Klotho gene expression and protein immunostaining in term (T-SGA y T-AGA) and preterm (PT-SGA y PT-AGA) human placentas. In addition, we assessed the effect of Klotho on the IGF-IR and AKT activation induced by IGF-I.Methods: Placentas (n = 1 17) from 32 T-SGA (birth weight (BW) = −1.74 ± 0.08 SDS), 37 T-AGA (BW = 0.12 ± 0.12 SDS), 20 PT-SGA (BW = −2.08 ± 0.14 SDS), and 28 PT-AGA (BW = −0.43 ± 0.13 SDS) newborns were collected. mRNA expression by RT-PCR in the chorionic (CP) and basal (BP) plates of the placentas, and the presence of Klotho was evaluated by immunohistochemistry (integral optical density, IOD). In addition, we developed placental explants that were incubated with IGF-I in the presence or absence of Klotho.Results: We found a lower mRNA expression and protein immunoreactivity of Klotho in the CP of SGA (term and preterm) compared with AGA placentas. We also observed a significant reduction in IGF-IR tyrosine activation induced by IGF-I 10 nM when preincubated with 2.0 nM of Klotho (2.4 ± 0.5 arbitrary units vs. 1.3 ± 0.3 AU), and similar results we observed on AKT and ERK42/44 activation.Conclusion: We describe for the first time that Klotho mRNA and protein varies according to fetal growth and gestational age. In addition, Klotho appears to down-regulate the activation induced by IGF-I on IGF-IR and AKT, suggesting that Klotho may be regulating IGF-I activity in human placentas according to intrauterine fetal growth.https://www.frontiersin.org/article/10.3389/fendo.2018.00797/fullplacentaklothoIGF-IIGF-IRfetal growthsmall for gestation age (SGA) |
| spellingShingle | Germán Iñiguez Pedro Gallardo Juan Jose Castro Rene Gonzalez Mirna Garcia Elena Kakarieka Sebastian San Martin Maria Cecilia Johnson Verónica Mericq Fernando Cassorla Klotho Gene and Protein in Human Placentas According to Birth Weight and Gestational Age Frontiers in Endocrinology placenta klotho IGF-I IGF-IR fetal growth small for gestation age (SGA) |
| title | Klotho Gene and Protein in Human Placentas According to Birth Weight and Gestational Age |
| title_full | Klotho Gene and Protein in Human Placentas According to Birth Weight and Gestational Age |
| title_fullStr | Klotho Gene and Protein in Human Placentas According to Birth Weight and Gestational Age |
| title_full_unstemmed | Klotho Gene and Protein in Human Placentas According to Birth Weight and Gestational Age |
| title_short | Klotho Gene and Protein in Human Placentas According to Birth Weight and Gestational Age |
| title_sort | klotho gene and protein in human placentas according to birth weight and gestational age |
| topic | placenta klotho IGF-I IGF-IR fetal growth small for gestation age (SGA) |
| url | https://www.frontiersin.org/article/10.3389/fendo.2018.00797/full |
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