Involvement of tazarotene-induced gene 1 in proliferation and differentiation of human adipose tissue-derived mesenchymal stem cells
Involvement of tazarotene-induced gene 1 in proliferation and differentiation of human adipose tissue-derived mesenchymal stem cells
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DOI：
10.1111/j.1365-2184.2008.00592.x
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发表时间：
2009-06-01
影响因子：
8.5
通讯作者：
Nagaya, N.
中科院分区：
文献类型：
--
作者：
Ohnishi, S.;Okabe, K.;Nagaya, N.
间充质干细胞（MSC）具有自我更新和多系分化潜能，骨髓来源的间充质干细胞已被应用于组织再生和修复。尽管脂肪组织来源的间充质干细胞（ASC）已经成为一种替代细胞来源，但关于内脏脂肪来源的间充质干细胞和皮下脂肪来源的间充质干细胞之间的生物学差异的信息很少。因此，我们旨在比较培养的人内脏ASC （VASC）和皮下ASC （SASC）的增殖和基因表达谱，并发现一个参与ASC增殖和分化的新基因。我们对培养的VASC和SASC进行了芯片分析，并研究了他zarotene诱导的基因1 （TIG1）在ASC增殖和分化中的作用，这是一个差异表达最多的基因。SASC的增殖速度超过VASC 10代，人、大鼠和小鼠VASC中TIG1表达持续上调。在人SASC中，过表达TIG1基因抑制细胞增殖，而通过siRNA敲低TIG1表达则促进细胞增殖。此外，TIG1基因在SASC中的过表达增强了其向脂肪细胞的分化，并促进过氧化物酶体增殖物激活受体γ和CCAAT/增强子结合蛋白α的上调。另一方面，TIG1在SASC中的过表达抑制了它们向骨细胞的分化和骨钙素的表达。TIG1在调节ASC的增殖和分化中起重要作用。
Mesenchymal stem cells (MSC) have both self-renewal and multilineage differentiation potential, and bone marrow-derived MSC have been applied for tissue regeneration and repair. Although adipose tissue-derived MSC (ASC) have emerged as an alternative cell source, little information is available regarding the biologic difference between ASC derived from visceral and subcutaneous fat. Therefore, we aimed to compare the proliferation and gene expression profile of cultured human visceral ASC (VASC) and subcutaneous ASC (SASC), and to identify a novel gene involved in proliferation and differentiation of ASC.We performed microarray analysis of cultured VASC and SASC, and investigated the role of tazarotene-induced gene 1 (TIG1), a most differentially expressed gene, in the proliferation and differentiation of ASC.SASC proliferated faster than VASC for over 10 passages, and TIG1 expression was consistently up-regulated in VASC of humans, rats and mice. Overexpression of the TIG1 gene in human SASC inhibited cell proliferation, whereas knockdown of TIG1 expression by siRNA promoted cell proliferation. In addition, overexpression of the TIG1 gene in SASC enhanced their differentiation into adipocytes, and promoted up-regulation of peroxisome proliferators-activated receptor gamma and CCAAT/enhancer binding protein alpha. On the other hand, TIG1 overexpression in SASC inhibited their differentiation into osteocytes and the expression of osteocalcin.TIG1 plays an important role in regulating proliferation and differentiation of ASC.