IFATS collection: Combinatorial peptides identify alpha5beta1 integrin as a receptor for the matricellular protein SPARC on adipose stromal cells.
The biological features of adipose stromal (stem) cells (ASC), which serve as progenitors for differentiated cells of white adipose tissue (WAT), are still largely undefined. In an initiative to identify functional ASC surface receptors, we screened a combinatorial library for peptide ligands binding to patient-derived ASC. We demonstrate that both primary and cultured human and mouse stromal cells express a conserved receptor targeted by peptides found to mimic SPARC, a matricellular protein that is required for normal WAT development. A signaling receptor for SPARC has not as yet been determined. By using the SPARC-mimicking peptides CMLAGWIPC (termed hPep) and CWLGEWLGC (termed mPep), isolated by panning on human and mouse cells, respectively, we identified the alpha5beta1 integrin complex as a candidate receptor for SPARC. On the basis of these results, we evaluated ASC responses to SPARC or SPARC-mimicking peptide exposure. Our results suggest that extracellular SPARC binds to alpha5beta1 integrin at sites of focal adhesions, an interaction disrupting firm attachment of ASC to extracellular matrix. We propose that SPARC-mediated mobilization of ASC through its effect on alpha5beta1 integrin complex provides a functional basis for the regulation of WAT body composition by SPARC. We also show that alpha5beta1 integrin is a potential target for ASC-selective intracellular delivery of bioactive peptides and gene therapy vectors directed by the SPARC-mimicking peptides. Disclosure of potential conflicts of interest is found at the end of this article.
Nie
Jing
J
Hope Heart Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
Chang
Benny
B
Traktuev
Dmitry O
DO
Sun
Jessica
J
March
Keith
K
Chan
Lawrence
L
Sage
E Helene
EH
Pasqualini
Renata
R
Arap
Wadih
W
Kolonin
Mikhail G
MG
D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D017209:Apoptosis; D055511:CCN Intercellular Signaling Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D004705:Endocytosis; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D039081:Integrin alpha5beta1 / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D015676:Osteonectin / Q000737:chemistry / Q000378:metabolism*; D019151:Peptide Library; D010449:Peptide Mapping; D010455:Peptides / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
D055511:CCN Intercellular Signaling Proteins; D039081:Integrin alpha5beta1; D015676:Osteonectin; D019151:Peptide Library; D010455:Peptides