Specific oxylipins enhance vertebrate hematopoiesis via the receptor GPR132.

Proceedings of the National Academy of Sciences of the United States of America
Jamie L LahvicLeonard I Zon

Abstract

Epoxyeicosatrienoic acids (EETs) are lipid-derived signaling molecules with cardioprotective and vasodilatory actions. We recently showed that 11,12-EET enhances hematopoietic induction and engraftment in mice and zebrafish. EETs are known to signal via G protein-coupled receptors, with evidence supporting the existence of a specific high-affinity receptor. Identification of a hematopoietic-specific EET receptor would enable genetic interrogation of EET signaling pathways, and perhaps clinical use of this molecule. We developed a bioinformatic approach to identify an EET receptor based on the expression of G protein-coupled receptors in cell lines with differential responses to EETs. We found 10 candidate EET receptors that are expressed in three EET-responsive cell lines, but not expressed in an EET-unresponsive line. Of these, only recombinant GPR132 showed EET-responsiveness in vitro, using a luminescence-based β-arrestin recruitment assay. Knockdown of zebrafish gpr132b prevented EET-induced hematopoiesis, and marrow from GPR132 knockout mice showed decreased long-term engraftment capability. In contrast to high-affinity EET receptors, GPR132 is reported to respond to additional hydroxy-fatty acids in vitro, and we found th...Continue Reading

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Citations

Nov 27, 2019·Pharmacology Research & Perspectives·James R FosterAndrew J Brown
May 19, 2019·International Journal of Molecular Sciences·Andreas LoewKarsten-H Weylandt
Jul 25, 2019·Frontiers in Pharmacology·Ingrid Fleming
Nov 5, 2019·Frontiers in Pharmacology·Tabea Osthues, Marco Sisignano
Oct 31, 2020·Antioxidants & Redox Signaling·Jan DudekChristoph Maack
Jan 4, 2020·Prostaglandins & Other Lipid Mediators·Laila R B Dos Santos, Ingrid Fleming
Aug 28, 2021·Cells·Marco SisignanoGerd Geisslinger

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