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

被引：13
作者：
Njaine, Brian [1 ]
Rocha-Martins, Mauricio [1 ]
Vieira-Vieira, Carlos H. [1 ]
Barbosa De-Melo, Luiz D. [2 ]
Linden, Rafael [1 ]
Braas, Karen [3 ]
May, Victor [3 ]
Martins, Rodrigo A. P. [4 ]
Silveira, Mariana S. [1 ]
机构：
[1] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Ilha Fundao, BR-21941902 Rio De Janeiro, Brazil
[2] IFRJ, Dept Biotecnol, Rio De Janeiro, Brazil
[3] Univ Vermont, Coll Med, Dept Anat & Neurobiol, Burlington, VT 05405 USA
[4] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, BR-21941902 Rio De Janeiro, Brazil
来源：
JOURNAL OF MOLECULAR NEUROSCIENCE | 2014年 / 54卷 / 03期
关键词：
Klf4; Cell cycle; Cyclin D1; Neuropeptide; PACAP; Retina; KRUPPEL-LIKE FACTOR-4; DEVELOPING CEREBRAL-CORTEX; BINDING-PROTEIN; CYCLIC-AMP; TUMOR-SUPPRESSOR; SONIC-HEDGEHOG; TGF-ALPHA; IN-VITRO; PACAP; EXPRESSION;
D O I：
10.1007/s12031-014-0299-2
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
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.
引用
收藏
页码：430 / 442
页数：13
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