Descriptive and functional characterization of epidermal growth factorlike domain 8 in mouse cortical thymic epithelial cells by integrated analysis of gene expression signatures and networks.
Int J Mol Med
; 47(3)2021 03.
Article
in En
| MEDLINE
| ID: mdl-33448309
ABSTRACT
Epidermal growth factorlike domain 8 (EGFL8), a newly identified member of the EGFL family, and plays negative regulatory roles in mouse thymic epithelial cells (TECs) and thymocytes. However, the role of EGFL8 in these cells remains poorly understood. In the present study, in order to characterize the function of EGFL8, genomewide expression profiles in EGFL8overexpressing or silenced mouse cortical TECs (cTECs) were analyzed. Microarray analysis revealed that 458 genes exhibited a >2fold change in expression levels in the EGFL8overexpressing vs. the EGFL8silenced cTECs. Several genes involved in a number of cellular processes, such as the cell cycle, proliferation, growth, migration and differentiation, as well as in apoptosis, reactive oxygen species generation, chemotaxis and immune responses, were differentially expressed in the EGFL8overexpressing or silenced cTECs. WST1 analysis revealed that that the overexpression of EGFL8 inhibited cTEC proliferation. To investigate the underlying mechanisms of EGFL8 in the regulation of cTEC function, genes related to essential cellular functions were selected. Reverse transcriptionpolymerase chain reaction analysis revealed that EGFL8 knockdown upregulated the expression of cluster differentiation 74 (CD74), Fas ligand (FasL), CXC motif chemokine ligand 5 (CXCL5), CXCL10, CXCL16, CC motif chemokine ligand 20 (CCL20), vascular endothelial growth factorA (VEGFA), interferon regulatory factor 7 (Irf7), insulinlike growth factor binding protein4 (IGFBP4), thrombospondin 1 (Thbs1) and nuclear factor κB subunit 2 (NFκB2) genes, and downregulated the expression of angiopoietinlike 1 (Angptl1), and neuropilin1 (Nrp1) genes. Additionally, EGFL8 silencing enhanced the expression of antiapoptotic molecules, such as Bcell lymphoma2 (Bcl2) and Bclextra large (BclxL), and that of cell cycleregulating molecules, such as cyclindependent kinase 1 (CDK1), CDK4, CDK6 and cyclin D1. Moreover, gene network analysis revealed that EGFL8 exerted negative effects on VEGFA gene expression. Hence, the altered expression of several genes associated with EGFL8 expression in cTECs highlights the important physiological processes in which EGFL8 is involved, and provides insight into its biological functions.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thymus Gland
/
Calcium-Binding Proteins
/
Gene Expression Regulation
/
Gene Expression Profiling
/
Epithelial Cells
/
EGF Family of Proteins
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Int J Mol Med
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Year:
2021
Document type:
Article