title: Proteolytic Isoforms of SPARC Induce Adipose Stromal Cell Mobilization in Obesity.
abstract: Adipose stromal cells (ASC) are mesenchymal adipocyte progenitors that reside in the peri-endothelium of fat tissue. ASC mobilization and migration accompany white adipose tissue (WAT) remodeling and pathological conditions. Mechanisms regulating ASC trafficking are largely unknown. We previously reported that binding of the matricellular protein secreted protein acidic and rich in cysteine (SPARC) to β1 integrin on ASC surface induces their motility. Here, we show that SPARC is required for ASC mobilization. We report two SPARC proteolytic isoforms, C-SPARC (lacking the N terminus) and N-SPARC (lacking the C terminus), generated in mesenteric WAT of obese mice. C-SPARC, but not N-SPARC, binds to β1 integrin on ASC, while N-SPARC preferentially binds to the extracellular matrix (ECM) and blocks ECM/integrin interaction. Interestingly, both C-SPARC and N-SPARC induce ASC deadhesion from the ECM, which is associated with modulation of integrin-dependent FAK-ERK signaling and integrin-independent ILK-Akt signaling. We show that these SPARC isoforms, acting on ASC through distinct mechanisms, have an additive effect in inducing ASC migration.
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, 77030, USA.
authors.forename: Chieh
authors.initials: C
authors.lastname: Tseng
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, 77030, USA.
authors.forename: Mikhail G
authors.initials: MG
authors.lastname: Kolonin
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000473:pathology*; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D039482:Integrin alpha5; D019012:Integrin beta1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008969:Molecular Sequence Data; D009765:Obesity / Q000378:metabolism* / Q000473:pathology*; D015676:Osteonectin / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D059748:Proteolysis; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases; D039482:Integrin alpha5; D019012:Integrin beta1; D015676:Osteonectin; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK
keywords: Adipose stromal cells; Mobilization; Obesity; Secreted protein acidic and rich in cysteine