Pleiotropic Functions of Pituitary Adenylyl Cyclase-Activating Polypeptide on Retinal Ontogenesis: Involvement of KLF4 in the Control of Progenitor Cell Proliferation

被引：0
作者：
Brian Njaine
Maurício Rocha-Martins
Carlos H. Vieira-Vieira
Luiz D. Barbosa De-Melo
Rafael Linden
Karen Braas
Victor May
Rodrigo A. P. Martins
Mariana S. Silveira
机构：
[1] Universidade Federal do Rio de Janeiro,Instituto de Biofísica Carlos Chagas Filho
[2] Instituto Federal do Rio de Janeiro,Departamento de Biotecnologia
[3] IFRJ,Department of Anatomy and Neurobiology
[4] University of Vermont College of Medicine,Instituto de Ciências Biomédicas
[5] Universidade Federal do Rio de Janeiro,undefined
[6] Max-Planck-Institut für Herz- und Lungenforschung,undefined
来源：
Journal of Molecular Neuroscience | 2014年 / 54卷
关键词：
Klf4; Cell cycle; Cyclin D1; Neuropeptide; PACAP; Retina;
D O I：
暂无
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学科分类号：
摘要：
We showed previously that the neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP) negatively regulates proliferation of postnatal rat retinal progenitor cells through the downregulation of cyclin D1 in a cAMP/protein kinase A dependent manner. In the present study, we describe by microarray analysis several putative PACAP targets regulated by different transcription factor families. One of these families is the Sp/Klf family of transcriptional factors capable of regulating cyclin D1, and among members, we demonstrate by immunocytochemistry that KLF4 is expressed throughout rat retinal development by retinal progenitor cells and in most differentiated cell types. Using retinal explants preparations, PACAP treatment can transiently increase Klf4 mRNA levels; from electrophoretic mobility shift assays, PACAP is also able to increase the nuclear KLF4 content. From these results, we suggest that KLF4 may be involved in the anti-proliferative effects of PACAP as one mechanism regulating progenitor cell transition from proliferation to differentiation throughout retinal development.
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页码：430 / 442
页数：12
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  • [1] Anchan RM(1995)Transforming growth factor-beta-3 is mitogenic for rat retinal progenitor cells in vitro J Neurobiol 28 133-145
  • [2] Reh TA(1991)EGF and TGF-alpha stimulate retinal neuroepithelial cell proliferation in vitro Neuron 6 923-936
  • [3] Anchan RM(2011)Effects of PACAP in UV-A radiation-induced retinal degeneration models in rats J Mol Neurosci 43 51-57
  • [4] Reh TA(2009)Effects of pituitary adenylate cyclase activating polypeptide and its fragments on retinal degeneration induced by neonatal monosodium glutamate treatment Ann N Y Acad Sci 1163 348-352
  • [5] Angello J(2011)Pituitary adenylate cyclase-activating peptide induces long-lasting neuroprotection through the induction of activity-dependent signaling via the cyclic AMP response element-binding protein-regulated transcription co-activator 1 J Neurochem 118 365-378
  • [6] Balliet A(2005)Pituitary adenylate cyclase-activating polypeptide (PACAP) can act as determinant of the tyrosine hydroxylase phenotype of dopaminergic cells during retina development Brain Res Dev Brain Res 156 193-201
  • [7] Walker M(2007)Microarray analyses of pituitary adenylate cyclase activating polypeptide (PACAP)-regulated gene targets in sympathetic neurons Peptides 28 1856-1870
  • [8] Atlasz T(2002)Pituitary adenylate cyclase activating polypeptide anti-mitogenic signaling in cerebral cortical progenitors is regulated by p57Kip2-dependent CDK2 activity J Neurosci 22 1583-1591
  • [9] Szabadfi K(1999)The roles of intrinsic and extrinsic cues and bHLH genes in the determination of retinal cell fates Curr Opin Neurobiol 9 37-46
  • [10] Kiss P(2001)Kruppel-like factor 4 (gut-enriched Kruppel-like factor) inhibits cell proliferation by blocking G1/S progression of the cell cycle J Biol Chem 276 30423-30428
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