TGFβ signaling reinforces pericyte properties of the non-endocrine mouse pituitary cell line TtT/GF.
TGFβ signaling reinforces pericyte properties of the non-endocrine mouse pituitary cell line TtT/GF.
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TGFβ 信号传导增强非内分泌小鼠垂体细胞系 TtT/GF 的周细胞特性。
DOI：
10.1007/s00441-017-2758-x
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Kato Y.
中科院分区：
文献类型：
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作者：
Tsukada T;Yoshida S;Kito K;Fujiwara K;Yako H;Horiguchi K;Isowa Y;Yashiro T;Kato T;Kato Y.
小鼠非内分泌TTT/GF细胞系来源于放射甲状旁腺切除术诱发的垂体腺瘤。除形态特征外，由于细胞呈S100β阳性，因此被认为是毛囊星状细胞的模型。然而，我们最近的基因芯片分析表明，与滤泡星状细胞相比，TTT/GF细胞可能不是终末分化的，因为它们与干细胞/祖细胞、血管内皮细胞和周细胞有一些共同的特性。本研究探讨转化生长因子-β(TGFR-β)能否诱导这些细胞进一步分化。结果表明，逆转录-聚合酶链式反应结果显示，TTT/GF细胞表达Tgfbr1、Tgfbr2、Tgfbr3和Tgfb1-3的β受体和β配体。Smad2是转化生长因子β途径的细胞间信号分子，在转化生长因子β信号转导过程中定位于细胞核。此外，转化生长因子β诱导细胞集落形成，这一作用可被转化生长因子β受体I抑制剂(SB431542)完全阻断。实时定量聚合酶链式反应分析显示，转化生长因子β下调干细胞标记物Sox2和CD34，上调周细胞标记物Nestin和NG2。用小鼠垂体组织进行双重免疫组织化学染色证实，在周细胞定位的血管周围区域存在Nestin/NG2双阳性细胞。我们的结果提示TTT/GF细胞对转化生长因子β信号有反应，这与细胞集落形成和周细胞分化有关。由于周细胞在其他组织中调节血管生成、肿瘤发生和干/祖细胞，TTT/GF细胞可能成为研究垂体周细胞在生理和病理过程中作用的有用模型。
The non-endocrine TtT/GF mouse pituitary cell line was derived from radiothyroidectomy-induced pituitary adenoma. In addition to morphological characteristics, because the cells are S100β-positive, they have been accepted as a model of folliculostellate cells. However, our recent microarray analysis indicated that, in contrast to folliculostellate cells, TtT/GF cells might not be terminally differentiated, as they share some properties with stem/progenitor cells, vascular endothelial cells and pericytes. The present study investigates whether transforming growth factor beta (TGFβ) can elicit further differentiation of these cells. The results showed that canonical (Tgfbr1andTgfbr2) and non-canonical TGFβ receptors (Tgfbr3) as well as all TGFβ ligands (Tgfb1–3) were present in TtT/GF cells, based on reverse transcription PCR. SMAD2, an intercellular signaling molecule of the TGFβ pathway, was localized in the nucleus upon TGFβ signaling. Furthermore, TGFβ induced cell colony formation, which was completely blocked by a TGFβ receptor I inhibitor (SB431542). Real-time PCR analysis indicated that TGFβ downregulated stem cell markers (Sox2andCd34) and upregulated pericyte markers (Nestin and Ng2). Double immunohistochemistry using mouse pituitary tissue confirmed the presence of NESTIN/NG2 double-positive cells in perivascular areas where pericytes are localized. Our results suggest that TtT/GF cells are responsive to TGFβ signaling, which is associated with cell colony formation and pericyte differentiation. As pericytes have been shown to regulate angiogenesis, tumorigenesis and stem/progenitor cells in other tissues, TtT/GF cells could be a useful model to study the role of pituitary pericytes in physiological and pathological processes.