Teruel T, Valverde A M, Benito M, Lorenzo M
Departamento de Bioquímica y Biología Molecular, Centro Mixto, Universidad Complutense, Madrid, Spain.
J Cell Physiol. 1996 Mar;166(3):577-84. doi: 10.1002/(SICI)1097-4652(199603)166:3<577::AID-JCP12>3.0.CO;2-4.
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.
与静止细胞相比，转化生长因子β1（TGF-β1）存在24或48小时可刺激DNA合成、细胞周期S + G2/M期的细胞百分比以及细胞数量。TGF-β1（1 pM）的促有丝分裂能力与10%胎牛血清（FCS）相似。与静止细胞相比，TGF-β1作用48小时可使含（3H）胸腺嘧啶核苷标记细胞核的细胞百分比增加5倍。此外，单个胎儿棕色脂肪细胞呈现其典型的多泡脂肪滴表型，对TGF-β1产生反应后，（3H）胸腺嘧啶核苷标记细胞核呈阳性。而且，与静止细胞相比，TGF-β1在4小时和8小时诱导了一组完整的增殖相关基因的mRNA表达，如c-fos（30分钟）、c-myc和β-肌动蛋白（2小时），以及H-ras、cdc2激酶和葡萄糖6-磷酸脱氢酶（G6PD）。同时，TGF-β1作用12小时使增殖细胞核抗原（PCNA）的蛋白质含量增加6倍，p21-ras增加2倍。虽然我们的结果表明TGF-β1诱导了与细胞增殖相关的早期基因的表达，但TGF-β1在诱导胎儿棕色脂肪细胞增殖中可能作为有丝分裂原或存活因子发挥作用。
