EGFL6 is increasingly expressed in human obesity and promotes proliferation of adipose tissue-derived stromal vascular cells.
With increasing rates of obesity driving the incidence of type 2 diabetes and cardiovascular diseases to epidemic levels, understanding of the biology of adipose tissue expansion is a focus of current research. Identification and characterization of secreted proteins of the adipose tissue could provide further insights into the function of adipose tissue and might help to therapeutically influence the development of obesity and associated metabolic disorders. In the present study, we identified human epidermal growth factor-like domain multiple-6 (EGFL6) as an adipose tissue-secreted protein. EGFL6 expression in human subcutaneous adipose tissue significantly increased with obesity and decreased after weight loss. Further, expression and secretion of EGFL6 increased with in vitro differentiation of human preadipocytes, suggesting that mature adipocytes are the main source of EGFL6. Containing epidermal growth factor (EGF)-like repeats, an Arg-Gly-Asp (RGD) integrin binding motif and a mephrin, A5 protein and receptor protein-tyrosine phosphatase mu (MAM) domain, EGFL6 was suggested to be an extra-cellular matrix protein. Recombinant human EGFL6 protein mediated cell adhesion of human adipose tissue-derived stromal vascular cells (AD-SVC) in an RGD-dependent manner. FACS analyses revealed specific binding of the protein to the cell surface of AD-SVC with the binding being predominantly mediated by the EGF-like repeats. Recombinant EGFL6 enhanced proliferation of human AD-SVC as measured by MTS assay and [(14)C]-thymidine incorporation. These results indicate that human EGFL6 is a paracrine/autocrine growth factor of adipose tissue up-regulated in obesity and potentially involved in the process of adipose tissue expansion and the development of obesity.
Oberauer
Rupert
R
Department of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
Rist
Wolfgang
W
Lenter
Martin C
MC
Hamilton
Bradford S
BS
Neubauer
Heike
H
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D049109:Cell Proliferation; D002469:Cell Separation; D002853:Chromatography, Liquid; D017077:Culture Media, Conditioned; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D015431:Weight Loss
D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; C403518:EGFL6 protein, human; D008562:Membrane Glycoproteins