Systemic and placental α-klotho: Effects of preeclampsia in the last trimester of gestation

Loichinger, Matthew; Towner, Dena; Thompson, Karen; Ahn, Hyeong Jun; Bryant‐Greenwood, Gillian D.

doi:10.1016/j.placenta.2016.03.004

Cited by 26 publications

(13 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Plasma samples were previously used for sFlt-1 measurement [30]. Visfatin/Nampt in plasma was measured by ELISA (Phoenix Pharmaceuticals, Burlingame, CA).…”

Section: Methodsmentioning

confidence: 99%

Protective proteins and telomere length in placentas from patients with pre-eclampsia in the last trimester of gestation

et al. 2017

Self Cite

View full text Add to dashboard Cite

Introduction Visfatin/nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in energy metabolism and sirtuins, SIRT1 and SIRT3, which are NAD-dependent deacetylases, are critical for cellular function. All three either regulate or are regulated by intracellular NAD+ levels and therefore available cellular energy, important for placental cell survival and successful pregnancy. This study investigates whether these protective proteins are involved in the placental pathophysiology of pre-eclampsia (PE) and if they are associated with 8-oxo-deoxyguanosine (8OHdG), a marker of oxidative damage or with placental telomere length. Methods Maternal blood and placental samples were collected from 31 patients with PE and 30 controls between 31 and 40 weeks gestation. Quantitative immunohistochemistry was performed on placental specimens for visfatin/Nampt, SIRT1, SIRT3, and nuclear 8OHdG. Plasma visfatin was measured by ELISA and telomere length by Southern blot analysis of telomere restriction fragments. Results Visfatin/Nampt and SIRT1 in syncytiotrophoblast decreased in PE compared to controls (p < 0.0001, p = 0.004 respectively). SIRT3 decreased in PE most significantly at preterm (p = 0.002). 8OHdG was only significantly lower in preterm controls compared to term controls (p = 0.01) and correlated with SIRT1 in all samples (r = 0.27). Telomere length was not different in PE and controls. Discussion Decreased visfatin/Nampt, SIRT1 and SIRT3 in syncytiotrophoblast in PE suggests a lack of placental reserve in metabolic energy efficiency, increased inflammation, and lower resistance to environmental stressors. However, there was little effect on nuclear function, or evidence of genomic DNA damage, which would lead to cellular senescence and death.

show abstract

“…Plasma samples were previously used for sFlt-1 measurement [30]. Visfatin/Nampt in plasma was measured by ELISA (Phoenix Pharmaceuticals, Burlingame, CA).…”

Section: Methodsmentioning

confidence: 99%

Protective proteins and telomere length in placentas from patients with pre-eclampsia in the last trimester of gestation

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Placental expression of Klotho is also detected by in situ hybridization ( Figure 3B). At both mRNA and protein level, Klotho is expressed predominantly in syncytiotrophoblasts [95,[145][146][147][148]…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Tissue expression and source of circulating αKlotho

Olauson

Mencke

Hillebrands

et al. 2017

Bone

View full text Add to dashboard Cite

αKlotho (Klotho), a type I transmembrane protein and a coreceptor for Fibroblast Growth Factor-23, was initially thought to be expressed only in a limited number of tissues, most importantly the kidney, parathyroid gland and choroid plexus. Emerging data may suggest a more ubiquitous Klotho expression pattern which has prompted reevaluation of the restricted Klotho paradigm. Herein we systematically review the evidence for Klotho expression in various tissues and cell types in humans and other mammals, and discuss potential reasons behind existing conflicting data. Based on current literature and tissue expression atlases, we propose a classification of tissues into high, intermediate and low/absent Klotho expression. The functional relevance of Klotho in organs with low expression levels remain uncertain and there is currently limited data on a role for membrane-bound Klotho outside the kidney. Finally, we review the evidence for the tissue source of soluble Klotho, and conclude that the kidney is likely to be the principal source of circulating Klotho in physiology.

show abstract

“…This lower Klotho protein immunodetection was also reported in placentas from women with preeclampsia (PE) compared with controls (18). However, Loichinger MH et al (14) reported no differences in Klotho protein expression between PE and control placentas, but this study did not investigate Klotho placental distribution assessed in both chorionic and basal plates as we did.…”

Section: Discussionmentioning

confidence: 68%

“…Recently, it has been documented that α-Klotho concentrations are increased in serum from mothers with preeclampsia (PE) from 32 to 40 weeks of gestation. However, the authors did not find differences in placental Klotho protein expression between PE and control mothers (14).…”

Section: Introductionmentioning

confidence: 78%

“…It is. (14) reported higher serum Klotho levels in pregnant compared with non-pregnant women and higher levels of Klotho in cord blood compared with serum levels observed at 4 days of life, suggesting that Klotho is derived from the placenta (13, 14). Our findings are in accordance with a recently study reported by Fan et al (18) who observed lower Klotho cord blood levels in gestations complicated by preeclampsia (PE), PE occurs in approximately 10% of all pregnancies and is characterized by a high incidence of intrauterine growth restriction.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Klotho Gene and Protein in Human Placentas According to Birth Weight and Gestational Age

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

Systemic and placental α-klotho: Effects of preeclampsia in the last trimester of gestation

Cited by 26 publications

References 42 publications

Protective proteins and telomere length in placentas from patients with pre-eclampsia in the last trimester of gestation

Protective proteins and telomere length in placentas from patients with pre-eclampsia in the last trimester of gestation

Tissue expression and source of circulating αKlotho

Klotho Gene and Protein in Human Placentas According to Birth Weight and Gestational Age

Contact Info

Product

Resources

About