Transforming growth factor β1 induces mitogenesis in fetal rat brown adipocytes

Abstract

The presence of transforming growth factor β1 (TGF-β1) for 24 or 48 h stimulated DNA synthesis, the percentage of cells in the S + G2/M phases of the cell cycle, and cell number, as compared to quiescent cells. The mitogenic capacity of TGF-β1 (1 pM) was similar to that shown by 10% fetal calf serum (FCS). TGF-β1 for 48 h increased by 5-fold the percentage of cells containing (3H)thymidine-labeled nuclei as compared to quiescent cells. In addition, single fetal brown adipocytes, showing their typical multilocular fat droplets phenotype, become positive for (3H)thymidme-labeled nuclei in response to TGF-β1. Moreover, TGF-β1 induced the mRNA expression of a complete set of proliferation-related genes, such as c-fos (30 min), c-myc and β-actin (2 h), and H-ras, cdc2 kinase, and glucose 6-phosphate dehydrogenase (G6PD) at 4 and 8 h, as compared to quiescent cells. Concurrently, TGF-β1 for 12 h increased the protein content of proliferating cellular nuclear antigen (PCNA) by 6-fold and p21-ras by 2-fold. Although our results demonstrate that TGF-β1 induces the expression of very early genes related to cell proliferation, TGF-β1 could be acting either as a mitogen or as a survival factor to induce proliferation in fetal brown adipocytes.