IFATS collection

Combinatorial peptides identify α5β1 integrin as a receptor for the matricellular protein SPARC on adipose stromal cells

Jing Nie, Benny Chang, Dmitry Traktuev, Jessica Sun, Keith March, Lawrence Chan, E. Helene Sage, Renata Pasqualini, Wadih Arap, Mikhail G. Kolonin

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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 α5β1 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 α5β1 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 α5β1 integrin complex provides a functional basis for the regulation of WAT body composition by SPARC. We also show that α5β1 integrin is a potential target for ASC-selective intracellular delivery of bioactive peptides and gene therapy vectors directed by the SPARC-mimicking peptides.

Original languageEnglish
Pages (from-to)2735-2745
Number of pages11
JournalStem Cells
Volume26
Issue number10
DOIs
StatePublished - Oct 2008

Fingerprint

Stromal Cells
Integrins
White Adipose Tissue
Peptides
Proteins
Stem Cells
Peptide Library
Focal Adhesions
Peptide Receptors
Body Composition
Genetic Therapy
Extracellular Matrix
Ligands

Keywords

  • Adipose stromal cells
  • Extracellular matrix
  • Mobilization
  • Peptide phage display

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

IFATS collection : Combinatorial peptides identify α5β1 integrin as a receptor for the matricellular protein SPARC on adipose stromal cells. / Nie, Jing; Chang, Benny; Traktuev, Dmitry; Sun, Jessica; March, Keith; Chan, Lawrence; Sage, E. Helene; Pasqualini, Renata; Arap, Wadih; Kolonin, Mikhail G.

In: Stem Cells, Vol. 26, No. 10, 10.2008, p. 2735-2745.

Research output: Contribution to journalArticle

Nie, Jing ; Chang, Benny ; Traktuev, Dmitry ; Sun, Jessica ; March, Keith ; Chan, Lawrence ; Sage, E. Helene ; Pasqualini, Renata ; Arap, Wadih ; Kolonin, Mikhail G. / IFATS collection : Combinatorial peptides identify α5β1 integrin as a receptor for the matricellular protein SPARC on adipose stromal cells. In: Stem Cells. 2008 ; Vol. 26, No. 10. pp. 2735-2745.
@article{78d539ba3c60480eb3fd3d7ee6754840,
title = "IFATS collection: Combinatorial peptides identify α5β1 integrin as a receptor for the matricellular protein SPARC on adipose stromal cells",
abstract = "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 α5β1 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 α5β1 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 α5β1 integrin complex provides a functional basis for the regulation of WAT body composition by SPARC. We also show that α5β1 integrin is a potential target for ASC-selective intracellular delivery of bioactive peptides and gene therapy vectors directed by the SPARC-mimicking peptides.",
keywords = "Adipose stromal cells, Extracellular matrix, Mobilization, Peptide phage display",
author = "Jing Nie and Benny Chang and Dmitry Traktuev and Jessica Sun and Keith March and Lawrence Chan and Sage, {E. Helene} and Renata Pasqualini and Wadih Arap and Kolonin, {Mikhail G.}",
year = "2008",
month = "10",
doi = "10.1634/stemcells.2008-0212",
language = "English",
volume = "26",
pages = "2735--2745",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "10",

}

TY - JOUR

T1 - IFATS collection

T2 - Combinatorial peptides identify α5β1 integrin as a receptor for the matricellular protein SPARC on adipose stromal cells

AU - Nie, Jing

AU - Chang, Benny

AU - Traktuev, Dmitry

AU - Sun, Jessica

AU - March, Keith

AU - Chan, Lawrence

AU - Sage, E. Helene

AU - Pasqualini, Renata

AU - Arap, Wadih

AU - Kolonin, Mikhail G.

PY - 2008/10

Y1 - 2008/10

N2 - 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 α5β1 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 α5β1 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 α5β1 integrin complex provides a functional basis for the regulation of WAT body composition by SPARC. We also show that α5β1 integrin is a potential target for ASC-selective intracellular delivery of bioactive peptides and gene therapy vectors directed by the SPARC-mimicking peptides.

AB - 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 α5β1 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 α5β1 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 α5β1 integrin complex provides a functional basis for the regulation of WAT body composition by SPARC. We also show that α5β1 integrin is a potential target for ASC-selective intracellular delivery of bioactive peptides and gene therapy vectors directed by the SPARC-mimicking peptides.

KW - Adipose stromal cells

KW - Extracellular matrix

KW - Mobilization

KW - Peptide phage display

UR - http://www.scopus.com/inward/record.url?scp=55049112979&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55049112979&partnerID=8YFLogxK

U2 - 10.1634/stemcells.2008-0212

DO - 10.1634/stemcells.2008-0212

M3 - Article

VL - 26

SP - 2735

EP - 2745

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 10

ER -