Adipose tissue-derived and bone marrow-derived mesenchymal cells develop into different lineage of steroidogenic cells by forced expression of steroidogenic factor 1
Adipose tissue-derived and bone marrow-derived mesenchymal cells develop into different lineage of steroidogenic cells by forced expression of steroidogenic factor 1
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DOI：
10.1210/en.2007-1808
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发表时间：
2008-09-01
期刊：
影响因子：
4.8
通讯作者：
Yanase, Toshihiko
中科院分区：
文献类型：
--
作者：
Gondo, Shigeki;Okabe, Taijiro;Yanase, Toshihiko
甾体生成因子1 (SF-1)/肾上腺素4结合蛋白是甾体生成以及肾上腺和性腺发育的重要核受体。我们之前已经阐明，腺病毒介导的SF-1的强制表达可以将长期培养的小鼠骨髓间充质细胞（BMCs）转化为acth反应性类固醇细胞。在本研究中，我们将这项工作扩展到脂肪组织来源的间充质细胞（AMCs），并将其与同一小鼠制备的bmc的类固醇生成能力进行了比较。几种细胞表面标记，包括潜在的间充质细胞标记，在两种细胞类型中是相同的，并且，正如预期的那样，强制表达SF-1导致AMCs转化为acth反应性类固醇细胞。然而，更详细的研究表明，AMCs的类固醇生成特性与BMCs有很大的不同，特别是在类固醇生成谱系中。在SF-1表达增加和/或维甲酸治疗的反应中，amc更容易产生肾上腺类固醇、皮质酮，而不是性腺类固醇、睾酮，而BMCs则相反。这种甾体生成谱在AMCs和BMCs之间的显著差异也可以通过甾体生成酶的变化来证明。这些新结果表明，AMCs在类固醇功能不全患者的自体细胞再生治疗中具有很好的应用前景，并且在制备间充质干细胞时需要根据目标进行适当的组织选择。AMCs和BMCs的不同类固醇生成能力可能为阐明组织或细胞特异性肾上腺和性腺类固醇细胞分化的机制提供了一个很好的模型。
Steroidogenic factor 1 (SF-1)/adrenal 4 binding protein is an essential nuclear receptor for steroidogenesis, as well as for adrenal and gonadal gland development. We have previously clarified that adenovirus-mediated forced expression of SF-1 can transform long-term cultured mouse bone marrow mesenchymal cells (BMCs) into ACTH-responsive steroidogenic cells. In the present study, we extended this work to adipose tissue-derived mesenchymal cells (AMCs) and compared its steroidogenic capacity with those of BMCs prepared from the identical mouse. Several cell surface markers, including potential mesenchymal cell markers, were identical in both cell types, and, as expected, forced expression of SF-1 caused AMCs to be transformed into ACTH-responsive steroidogenic cells. However, more elaborate studies revealed that the steroidogenic property of AMCs was rather different from that of BMCs, especially in steroidogenic lineage. In response to increased SF-1 expression and/or treatment with retinoic acid, AMCs were much more prone to produce adrenal steroid, corticosterone rather than gonadal steroid, testosterone, whereas the contrary was evident in BMCs. Such marked differences in steroidogenic profiles between AMCs and BMCs were also evident by the changes of steroidogenic enzymes. These novel results suggest a promising utility of AMCs for autologous cell regeneration therapy for patients with steroid insufficiency and also a necessity for appropriate tissue selection in preparing mesenchymal stem cells according to the aim. The different steroidogenic potency of AMCs or BMCs might provide a good model for the clarification of the mechanism of tissue-or cell-specific adrenal and gonadal steroidogenic cell differentiation.