Choroid plexus epithelial cells as a model to study nongenomic steroid signaling and its effect on ion channel function

Haoui, Monika; Petersen, Natalie; Björkgren, Ida; Chung, Dong-Hwa; Lishko, Polina V.

doi:10.1016/bs.mie.2021.03.004

Cited by 7 publications

(3 citation statements)

References 30 publications

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“…Recently, we reported that murine Kir7.1 expressed in the choroid plexus and retinal pigment epithelia is potently and specifically activated by progesterone (19,20) and that such activation is independent of G-protein regulation (20). This finding led us to compare the properties of human and murine Kir7.1 to verify whether human Kir7.1 can be regulated by progesterone in the similar manner.…”

Section: Results Kir 71 Is Expressed In Myometrial Smooth Muscle and ...mentioning

confidence: 98%

Kir7.1 is the physiological target for hormones and steroids that regulate uteroplacental function

Haoui

Vergara

Lishko

2023

Preprint

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Preterm birth is a multifactorial syndrome that is detrimental to the well-being of both the mother and the newborn. During normal gestation, the myometrium is maintained in a quiescent state by the action of progesterone. As a steroid hormone, progesterone is thought to modify uterine and placental morphology by altering gene expression, but a nongenomic mode of action has long been suspected. Here we reveal that progesterone activates both human and murine inwardly rectifying potassium channel Kir7.1, which is expressed in mammalian myometrial smooth muscle and placental pericytes during late gestation. Kir7.1 is also activated by compounds used to prevent premature labor, including the progestogens 17-alpha-hydroxyprogesterone caproate and dydrogesterone, revealing an unexpected mode of action for these drugs. Our results reveal that Kir7.1 is the molecular target of a number of endogenous and synthetic steroids that control uterine excitability and placental function, and is therefore a promising therapeutic target to control utero-placental physiology and support healthy pregnancy

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Section: Results Kir 71 Is Expressed In Myometrial Smooth Muscle and ...mentioning

confidence: 98%

Kir7.1 is the physiological target for hormones and steroids that regulate uteroplacental function

Haoui

Vergara

Lishko

2023

Preprint

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“…CP represents a convenient tissue to study the physiology of ion channels, particularly their regulation by steroid hormones via nongenomic mechanisms ( Haoui et al, 2021 ), because of the low expression of genomic steroid receptors in the adult CP ( Table 1 ). As is evident from CP gene expression analyses ( Data S1 ), several transient receptor potential ion channels, such as TRPM3 and TRPV4, were also found to be expressed in CP ( Millar et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

The epithelial potassium channel Kir7.1 is stimulated by progesterone

Björkgren

Mendoza

Chung

et al. 2021

Journal of General Physiology

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The choroid plexus (CP) epithelium secretes cerebrospinal fluid and plays an important role in healthy homeostasis of the brain. CP function can be influenced by sex steroid hormones; however, the precise molecular mechanism of such regulation is not well understood. Here, using whole-cell patch-clamp recordings from male and female murine CP cells, we show that application of progesterone resulted in specific and strong potentiation of the inwardly rectifying potassium channel Kir7.1, an essential protein that is expressed in CP and is required for survival. The potentiation was progesterone specific and independent of other known progesterone receptors expressed in CP. This effect was recapitulated with recombinant Kir7.1, as well as with endogenous Kir7.1 expressed in the retinal pigment epithelium. Current-clamp studies further showed a progesterone-induced hyperpolarization of CP cells. Our results provide evidence of a progesterone-driven control of tissues in which Kir7.1 is present.

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“…These cells are well-equipped with enzymes—cytochromes P450—needed for the metabolism of endogenous hydrophobic molecules and xenobiotics. 34 , 48 , 49 Presumably, they should express wide spectrum of receptors sensitive to metabolites produced locally or transferred from the peripheral blood. For instance, recent data suggest that CPECs as well as ependymal cells express lactate GPR81 receptors, 50 thereby they are able to sense lactate which is considered as a key molecule in intercellular metabolic coupling and brain plasticity.…”

Section: Complexity Of the Neurovascular Unit And Key Brain Tissue Ba...mentioning

confidence: 99%

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro?

Salmina,

Alexandrova,

Averchuk

et al. 2024

J Tissue Eng

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In vitro modeling of brain tissue is a promising but not yet resolved problem in modern neurobiology and neuropharmacology. Complexity of the brain structure and diversity of cell-to-cell communication in (patho)physiological conditions make this task almost unachievable. However, establishment of novel in vitro brain models would ultimately lead to better understanding of development-associated or experience-driven brain plasticity, designing efficient approaches to restore aberrant brain functioning. The main goal of this review is to summarize the available data on methodological approaches that are currently in use, and to identify the most prospective trends in development of neurovascular unit, blood-brain barrier, blood-cerebrospinal fluid barrier, and neurogenic niche in vitro models. The manuscript focuses on the regulation of adult neurogenesis, cerebral microcirculation and fluids dynamics that should be reproduced in the in vitro 4D models to mimic brain development and its alterations in brain pathology. We discuss approaches that are critical for studying brain plasticity, deciphering the individual person-specific trajectory of brain development and aging, and testing new drug candidates in the in vitro models.

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Choroid plexus epithelial cells as a model to study nongenomic steroid signaling and its effect on ion channel function

Cited by 7 publications

References 30 publications

Kir7.1 is the physiological target for hormones and steroids that regulate uteroplacental function

Kir7.1 is the physiological target for hormones and steroids that regulate uteroplacental function

The epithelial potassium channel Kir7.1 is stimulated by progesterone

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro?

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