1. Silencing of Fli1 Gene Mimics Effects of Preeclampsia and Induces Collagen Synthesis in Human Umbilical Arteries.
- Author
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Agalakova NI, Reznik VA, Ershov IA, Lupanova EA, Nadei OV, Ivanov DO, David Adair C, and Bagrov AY
- Subjects
- Animals, Collagen Type I metabolism, Female, Humans, Pregnancy, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Rats, Sodium-Potassium-Exchanging ATPase metabolism, Umbilical Arteries, Bufanolides metabolism, Pre-Eclampsia genetics, Pre-Eclampsia metabolism, Proto-Oncogene Protein c-fli-1 genetics
- Abstract
Background: Previously we demonstrated that in patients with preeclampsia elevated levels of endogenous Na/K-ATPase inhibitor, marinobufagenin, cause inhibition of Friend leukemia virus integration 1 (Fli1), a negative regulator of collagen-1 synthesis. We hypothesized that in vitro silencing of Fli1 in healthy human umbilical arteries would be associated with an increase in collagen-1 output, similar to the effect of preeclampsia in rat and human tissues., Methods: The isolated segments of healthy human umbilical arteries were tested for sensitivity to MBG and Fli1 silencing with Fli1 siRNA or control siRNA., Results: Following 24-hour incubation of arteries with nanomolar concentrations of marinobufagenin, Fli1 expression was inhibited 5-fold (P < 0.001), and synthesis of collagen-1 increased 3 times (P < 0.01). Twenty-four-hour incubation of umbilical artery fragments with Fli1 siRNA caused a dramatic decrease of Fli1 (7-fold; P < 0.001) and cytoplasmic PKC δ (4-fold; P < 0.001) expression in comparison to control siRNA or untreated control, followed by elevation in procollagen (3-fold; P < 0.001) and collagen-1 (3-fold; P < 0.001) levels in vascular tissue., Conclusions: Our results show that after silencing the Fli1 gene in healthy human umbilical arteries a new phenotype emerges which is typical for preeclampsia and is associated with vascular fibrosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2022
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