Involvement of AP-1 and C/EBPβ in upregulation of endothelin B (ETB) receptor expression in a rodent model of glaucoma

Autor: Hai Ying Ma, Alena Z. Minton, Shaoqing He, Dorota L. Stankowska, Xiangle Sun, Raghu R. Krishnamoorthy
Rok vydání: 2013
Předmět:
Male
Retinal Ganglion Cells
genetic structures
Proto-Oncogene Proteins c-jun
lcsh:Medicine
Gene Expression
0302 clinical medicine
Genes
Reporter
Gene expression
lcsh:Science
Receptor
Promoter Regions
Genetic
Regulation of gene expression
0303 health sciences
Multidisciplinary
Receptor
Endothelin A
Receptor
Endothelin B
Gene Knockdown Techniques
cardiovascular system
Endothelin receptor
circulatory and respiratory physiology
Protein Binding
Research Article
Biology
Retina
Cell Line
03 medical and health sciences
Downregulation and upregulation
Animals
Humans
RNA
Messenger
Transcription factor
Intraocular Pressure
030304 developmental biology
Messenger RNA
Binding Sites
CCAAT-Enhancer-Binding Protein-beta
lcsh:R
Promoter
Glaucoma
Molecular biology
eye diseases
Rats
Transcription Factor AP-1
Disease Models
Animal
Gene Expression Regulation
Mutation
030221 ophthalmology & optometry
lcsh:Q
sense organs
Zdroj: PLoS ONE
PLoS ONE, Vol 8, Iss 11, p e79183 (2013)
ISSN: 1932-6203
Popis: Previous studies showed that the endothelin B receptor (ETB) expression was upregulated and played a key role in neurodegeneration in rodent models of glaucoma. However, the mechanisms underlying upregulation of ETB receptor expression remain largely unknown. Using promoter-reporter assays, the 1258 bp upstream the human ETB promoter region was found to be essential for constitutive expression of ETB receptor gene in human non-pigmented ciliary epithelial cells (HNPE). The -300 to -1 bp and -1258 to -600 bp upstream promoter regions of the ETB receptor appeared to be the key binding regions for transcription factors. In addition, the crucial AP-1 binding site located at -615 to -624 bp upstream promoter was confirmed by luciferase assays and CHIP assays which were performed following overexpression of c-Jun in HNPE cells. Overexpression of either c-Jun or C/EBPβ enhanced the ETB receptor promoter activity, which was reflected in increased mRNA and protein levels of ETB receptor. Furthermore, knock-down of either c-Jun or C/EBPβ in HNPE cells was significantly correlated to decreased mRNA levels of both ETB and ETA receptor. These observations suggest that c-Jun and C/EBPβ are important for regulated expression of the ETB receptor in HNPE cells. In separate experiments, intraocular pressure (IOP) was elevated in one eye of Brown Norway rats while the corresponding contralateral eye served as control. Two weeks of IOP elevation produced increased expression of c-Jun and C/EBPβ in the retinal ganglion cell (RGC) layer from IOP-elevated eyes. The mRNA levels of c-Jun, ETA and ETB receptor were upregulated by 2.2-, 3.1- and 4.4-fold in RGC layers obtained by laser capture microdissection from retinas of eyes with elevated IOP, compared to those from contralateral eyes. Taken together, these data suggest that transcription factor AP-1 plays a key role in elevation of ETB receptor in a rodent model of ocular hypertension.
Databáze: OpenAIRE
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