Transdifferentiation of preadipose cells into smooth muscle-like cells: role of aortic carboxypeptidase-like protein.
Adipocyte differentiation involves dramatic cell shape alterations that are accompanied by changes in the expression of cytoskeletal and extracellular matrix (ECM) proteins. Aortic carboxypeptidase-like protein (ACLP) is a secreted protein associated with the extracellular matrix whose expression is induced during smooth muscle (SM) differentiation. We analyzed the expression of ACLP gene during adipocyte differentiation of 3T3-F442A, 3T3-L1, and Ob1771 preadipocytes. Our results show that ACLP mRNA and protein are expressed in growing cells and after commitment. Thereafter, their expression levels decrease, as opposed to that of aP2 and PPARgamma2. Consistent with these observations, ACLP mRNA is expressed in the stromal-vascular fraction of adipose tissue but not in the adipocyte fraction. Overexpression of ACLP in 3T3-F442A preadipocytes inhibits adipocyte differentiation at both morphological and molecular level. However, ACLP overexpression promotes transdifferentiation of preadipocytes into smooth muscle-like cells, which express specific markers such as SM22alpha, SM alpha-actin, SM-MHC, and caldesmon. These findings demonstrate that overexpression of a single extracellular matrix protein is sufficient to induce transdifferentiation and that ACLP may modulate the commitment of mesodermal cells into different lineages depending upon its pattern of expression.
Abderrahim-Ferkoune
Anissa
A
Developmental Biology and Cancer Research-UMR 6543 CNRS, Institute of Signaling, Faculté des Sciences, Parc Valrose, 06108 Nice Cedex 2, France.
Bezy
Olivier
O
Astri-Roques
Stéphanie
S
Elabd
Christian
C
Ailhaud
Gérard
G
Amri
Ez-Zoubir
EZ
D000199:Actins / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002268:Carboxypeptidases; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
C484818:AEBP1 protein, human; D000199:Actins; C112918:Aebp1 protein, mouse; D015415:Biomarkers; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C058992:Tagln protein, mouse; D014157:Transcription Factors; C051615:transgelin; D002268:Carboxypeptidases; D018995:Myosin Heavy Chains