Alterations in the TGFβ signaling pathway in myogenic progenitors with age
Alterations in the TGFβ signaling pathway in myogenic progenitors with age
复制标题
DOI：
10.1111/j.1474-9728.2004.00135.x
复制
发表时间：
2004-12-01
期刊：
影响因子：
7.8
通讯作者：
Peterson, CA
中科院分区：
文献类型：
--
作者：
Beggs, ML;Nagarajan, R;Peterson, CA
成肌前体细胞对有丝分裂后肌纤维的修复、维持和肥大是必需的。随着年龄的增长，脂肪沉积和纤维化导致肌肉的完整性和功能能力下降。在以前的研究中，我们报道了从老年小鼠获得的肌源性祖细胞中脂质积累增加，伴随着脂肪形成分化相关基因的上调。本研究旨在扩展我们对衰老如何影响肌源性祖细胞的命运和基因表达谱的理解。使用从分离自成年（8月龄）和老年（24月龄）DBA/2 JNIA小鼠的肌源性祖细胞提取的RNA进行Affyrin鼠U 74基因芯片分析。来自老年动物的细胞表现出直接或间接参与TGF β信号通路的许多基因的表达水平的重大改变。我们的数据表明，随着年龄的增长，肌源性祖细胞获得矛盾的表型，即基于TGF β诱导基因的过表达而被TGF β激活，但对外源性TGF β的分化抑制作用具有抗性。TGF β调节基因（如结缔组织生长因子）的过度表达可能在增加衰老肌肉纤维化中发挥作用。
Myogenic progenitors in adult muscle are necessary for the repair, maintenance and hypertrophy of post-mitotic muscle fibers. With age, fat deposition and fibrosis contribute to the decline in the integrity and functional capacity of muscles. In a previous study we reported increased accumulation of lipid in myogenic progenitors obtained from aged mice, accompanied by an up-regulation of genes involved in adipogenic differentiation. The present study was designed to extend our understanding of how aging affects the fate and gene expression profile of myogenic progenitors. Affymetrix murine U74 Gene-chip analysis was performed using RNA extracted from myogenic progenitors isolated from adult (8-month-old) and aged (24-month-old) DBA/2JNIA mice. The cells from the aged animals exhibited major alterations in the expression level of many genes directly or indirectly involved with the TGFbeta signaling pathway. Our data indicate that with age, myogenic progenitors acquire the paradoxical phenotype of being both TGFbeta activated based on overexpression of TGFbeta-inducible genes, but resistant to the differentiation-inhibiting effects of exogenous TGFbeta. The overexpression of TGFbeta-regulated genes, such as connective tissue growth factor, may play a role in increasing fibrosis in aging muscle.