Transdifferentiation of preadipose cells into smooth muscle-like cells: role of aortic carboxypeptidase-like protein

Anissa Abderrahim-Ferkoune; Olivier Bezy; Stéphanie Astri-Roques; Christian Elabd; Gérard Ailhaud; Ez-Zoubir Amri

doi:10.1016/j.yexcr.2003.10.020

Transdifferentiation of preadipose cells into smooth muscle-like cells: role of aortic carboxypeptidase-like protein

Exp Cell Res. 2004 Feb 15;293(2):219-28. doi: 10.1016/j.yexcr.2003.10.020.

Authors

Anissa Abderrahim-Ferkoune¹, Olivier Bezy, Stéphanie Astri-Roques, Christian Elabd, Gérard Ailhaud, Ez-Zoubir Amri

Affiliation

¹ Developmental Biology and Cancer Research-UMR 6543 CNRS, Institute of Signaling, Faculté des Sciences, Parc Valrose, 06108 Nice Cedex 2, France.

PMID: 14729459
DOI: 10.1016/j.yexcr.2003.10.020

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / metabolism
Adipocytes / cytology
Adipocytes / metabolism*
Animals
Biomarkers
Calmodulin-Binding Proteins / metabolism
Carboxypeptidases
Carrier Proteins / metabolism
Cell Differentiation / genetics*
Cell Lineage / genetics*
Extracellular Matrix Proteins / genetics
Extracellular Matrix Proteins / metabolism
Fatty Acid-Binding Protein 7
Fatty Acid-Binding Proteins
Gene Expression Regulation, Developmental / genetics
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / metabolism*
Mice
Microfilament Proteins / metabolism
Muscle Proteins / metabolism
Muscle, Smooth / cytology
Muscle, Smooth / metabolism*
Myosin Heavy Chains / metabolism
NIH 3T3 Cells
Neoplasm Proteins*
Nerve Tissue Proteins*
Proteins / genetics
Proteins / metabolism*
RNA, Messenger / metabolism
Receptors, Cytoplasmic and Nuclear / metabolism
Repressor Proteins
Transcription Factors / metabolism
Up-Regulation / genetics

Substances

AEBP1 protein, human
Actins
Aebp1 protein, mouse
Biomarkers
Calmodulin-Binding Proteins
Carrier Proteins
Extracellular Matrix Proteins
Fabp5 protein, mouse
Fabp7 protein, mouse
Fatty Acid-Binding Protein 7
Fatty Acid-Binding Proteins
Microfilament Proteins
Muscle Proteins
Neoplasm Proteins
Nerve Tissue Proteins
Proteins
RNA, Messenger
Receptors, Cytoplasmic and Nuclear
Repressor Proteins
Tagln protein, mouse
Transcription Factors
transgelin
Carboxypeptidases
Myosin Heavy Chains