Locked Out: Phoenixin-14 Does Not Cross a Stem-Cell-Derived Blood–Brain Barrier Model

Autor: Martha A. Schalla, Sabrina Oerter, Alevtina Cubukova, Marco Metzger, Antje Appelt-Menzel, Andreas Stengel
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Brain Sciences, Vol 13, Iss 7, p 980 (2023)
Druh dokumentu: article
ISSN: 2076-3425
DOI: 10.3390/brainsci13070980
Popis: Phoenixin-14 is a recently discovered peptide regulating appetite. Interestingly, it is expressed in the gastrointestinal tract; however, its supposed receptor, GPR173, is predominantly found in hypothalamic areas. To date, it is unknown how peripherally secreted phoenixin-14 is able to reach its centrally located receptor. To investigate whether phoenixin is able to pass the blood–brain barrier, we used an in vitro mono-culture blood–brain barrier (BBB) model consisting of brain capillary-like endothelial cells derived from human induced-pluripotent stem cells (hiPSC-BCECs). The passage of 1 nMol and 10 nMol of phoenixin-14 via the mono-culture was measured after 30, 60, 90, 120, 150, 180, 210, and 240 min using a commercial ELISA kit. The permeability coefficients (PC) of 1 nMol and 10 nMol phoenixin-14 were 0.021 ± 0.003 and 0.044 ± 0.013 µm/min, respectively. In comparison with the PC of solutes known to cross the BBB in vivo, those of phoenixin-14 in both concentrations are very low. Here, we show that phoenixin-14 alone is not able to cross the BBB, suggesting that the effects of peripherally secreted phoenixin-14 depend on a co-transport mechanism at the BBB in vivo. The mechanisms responsible for phoenixin-14′s orexigenic property along the gut–brain axis warrant further research.
Databáze: Directory of Open Access Journals
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