Pituitary adenylyl cyclase-activating polypeptide controls the proliferation of retinal progenitor cells through downregulation of cyclin D1

The European Journal of Neuroscience
Brian NjaineMariana S Silveira

Abstract

During retinal development, cell proliferation and exit from the cell cycle must be precisely regulated to ensure the generation of the appropriate numbers and proportions of the various retinal cell types. Previously, we showed that pituitary adenylyl cyclase-activating polypeptide (PACAP) exerts a neuroprotective effect in the developing retina of rats, through the cAMP-cAMP-dependent protein kinase (protein kinase A) (PKA) pathway. Here, we show that PACAP also regulates the proliferation of retinal progenitor cells. PACAP, PACAP-specific receptor (PAC1), and the receptors activated by both PACAP and vasoactive intestinal peptide (VIP), VPAC1 and VPAC2, are expressed during embryonic and postnatal development of the rat retina. Treatment of retinal explants with PACAP38 reduced the incorporation of [(3)H]thymidine as well as the number of 5-bromo-2'-deoxyuridine-positive and cyclin D1-positive cells. Pharmacological experiments indicated that PACAP triggers this antiproliferative effect through the activation of both PAC1 and VPACs, and the cAMP-PKA pathway. In addition, PACAP receptor activation decreased both cyclin D1 mRNA and protein content. Altogether, the data support the hypothesis that PACAP is a cell-extrinsic regu...Continue Reading

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Citations

Aug 1, 2013·Journal of Molecular Neuroscience : MN·Agata Grazia D'AmicoVelia D'Agata
May 31, 2014·Journal of Molecular Neuroscience : MN·Agata Grazia D'AmicoVelia D'Agata
Jan 23, 2016·Developmental Biology·Randy RinguetteValerie A Wallace
Jun 22, 2016·Anatomical Science International·Seiji ShiodaTomoya Nakamachi
Aug 27, 2016·Journal of Molecular Neuroscience : MN·Timea KvarikTamas Atlasz
Aug 28, 2016·Journal of Molecular Neuroscience : MN·A VaczyT Atlasz
Feb 23, 2019·Investigative Ophthalmology & Visual Science·Viktoria DenesRobert Gabriel
Aug 14, 2019·Development·Maurício Rocha-MartinsMariana S Silveira
Jan 7, 2021·Journal of Molecular Neuroscience : MN·Agata Grazia D'AmicoVelia D'Agata

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