Spred negatively regulates lens growth by modulating epithelial cell proliferation and fiber differentiation

Autor: Fatima Wazin, Frank J. Lovicu, Charles G. Bailey, Yue Feng, Alyssa Susanto, Guannan Zhao, John E.J. Rasko
Rok vydání: 2018
Předmět:
0301 basic medicine
MAP Kinase Signaling System
medicine.medical_treatment
Blotting
Western
Morphogenesis
Mice
Transgenic
Fibroblast growth factor
Transfection
Receptor tyrosine kinase
Adenoviridae
03 medical and health sciences
Cellular and Molecular Neuroscience
Mice
0302 clinical medicine
Lens
Crystalline
medicine
Animals
Phosphorylation
Fluorescent Antibody Technique
Indirect
Adaptor Proteins
Signal Transducing
Cell Proliferation
biology
Growth factor
Synexpression
Gene Expression Regulation
Developmental
Cell Differentiation
Epithelial Cells
Sensory Systems
Cell biology
Fibroblast Growth Factors
Mice
Inbred C57BL
Repressor Proteins
Ophthalmology
030104 developmental biology
medicine.anatomical_structure
Lens (anatomy)
SPRY2
030221 ophthalmology & optometry
biology.protein
Lens epithelial cell proliferation
Zdroj: Experimental eye research. 178
ISSN: 1096-0007
Popis: Spred, like Sprouty (Spry) and also Sef proteins, have been identified as important regulators of receptor tyrosine kinase (RTK)-mediated MAPK/ERK-signaling in various developmental systems, controlling cellular processes such as proliferation, migration and differentiation. Spreds are widely expressed during early embryogenesis, and in the eye lens, become more localised in the lens epithelium with later development, overlapping with other antagonists including Spry. Given the synexpression of Spreds and Spry in lens, in order to gain a better understanding of their specific roles in regulating growth factor mediated-signaling and cell behavior, we established and characterised lines of transgenic mice overexpressing Spred1 or Spred2, specifically in the lens. This overexpression of Spreds resulted in a small lens phenotype during ocular morphogenesis, retarding its growth by compromising epithelial cell proliferation and fiber differentiation. These in situ findings were shown to be dependent on the ability of Spreds to suppress MAPK-signaling, in particular FGF-induced ERK1/2-signaling in lens cells. This was validated in vitro using lens epithelial explants, that highlighted the overlapping role of Spreds with Spry2, but not Spry1. This study provides insights into the putative function of Spreds and Spry in situ, some overlapping and some distinct, and their importance in regulating lens cell proliferation and fiber differentiation contributing to lens and eye growth.
Databáze: OpenAIRE
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