Transforming growth factor beta 1 induces mitogenesis in fetal rat brown adipocytes.
The presence of transforming growth factor beta 1 (TGF-beta 1) 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-beta 1 (1 pM) was similar to that shown by 10% fetal calf serum (FCS). TGF-beta 1 for 48 h increased by 5-fold the percentage of cells containing (3H)thymidine-labeled nuclei as compared to quiescent cels. In addition, single fetal brown adipocytes, showing their typical multilocular fat droplets phenotype, become positive for (3H)thymidine-labeled nuclei in response to TGF-beta 1. Moreover, TGF-beta 1 induced the mRNA expression of a complete set of proliferation-related genes, such as c-fos (30 min), c-myc and beta-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-beta 1 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-beta 1 induces the expression of very early genes related to cell proliferation, TGF-beta 1 could be acting either as a mitogen or as a survival factor in induce proliferation to fetal brown adipocytes.
Teruel
T
T
Departamento de Bioquímica y Biología Molecular, Centro Mixto, Universidad Complutense, Madrid, Spain.
Valverde
A M
AM
Benito
M
M
Lorenzo
M
M
D017667:Adipocytes / Q000166:cytology*; D000273:Adipose Tissue / Q000166:cytology / Q000196:embryology; D000818:Animals; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005786:Gene Expression Regulation; D008934:Mitogens / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D008934:Mitogens; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004247:DNA; D016283:Proto-Oncogene Proteins p21(ras)