Down-regulation of aortic carboxypeptidase-like protein during the early phase of 3T3-L1 adipogenesis

Aortic carboxypeptidase-like protein (ACLP) is a 175-kDa protein that is expressed in vascular smooth muscle cells and contains a signal peptide sequence, a lysine- and proline-rich repeating motif, a discoidin-like domain with 35% identity to discoidin 1, and a carboxypeptidase-like domain that is 39% identical with carboxypeptidase E. It is secreted into the extracellular matrix and may play a role in abdominal wall development and dermal wound healing. ACLP is also expressed in adipose tissue, but at lower levels. In this study we demonstrate that ACLP protein and mRNA are severely down-regulated in the early phase of 3T3-L1 preadipocyte differentiation induced by insulin, dexamethasone, and isobutylmethylxanthine. Neither dexamethasone, isobutyl- methylxanthine, nor insulin treatment alone reduced the level of ACLP protein, suggesting that ACLP down-regulation is a differentiation-associated event. ACLP down-regulation coincided with the onset of the postconfluent mitotic clonal expansion phase of adipogenesis. In contrast, subconfluent 3T3-L1 cell proliferation did not alter ACLP expression, suggesting a specific linkage between ACLP and differentiation-induced clonal expansion. Stable overexpression of ACLP had no effect on preadipocyte differentiation assessed by triacylglycerol accumulation and peroxisome proliferator-activated receptor-gamma levels. The role of ACLP and its marked reduction during adipogenesis merit further study.