Characterization of dedifferentiating human mature adipocytes from the visceral and subcutaneous fat compartments: fibroblast-activation protein alpha and dipeptidyl peptidase 4 as major components of matrix remodeling.
Characterization of dedifferentiating human mature adipocytes from the visceral and subcutaneous fat compartments: fibroblast-activation protein alpha and dipeptidyl peptidase 4 as major components of matrix remodeling.
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DOI：
10.1371/journal.pone.0122065
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tchernof A
中科院分区：
文献类型：
--
作者：
Lessard J;Pelletier M;Biertho L;Biron S;Marceau S;Hould FS;Lebel S;Moustarah F;Lescelleur O;Marceau P;Tchernof A
成熟脂肪细胞可以逆转其表型成为成纤维细胞样细胞。这是通过天花板培养实现的，所产生的细胞称为去分化脂肪（DFAT）细胞，是多能的。除了这些细胞对再生医学的潜在价值外，去分化过程本身也引发了许多关于细胞可塑性和细胞行为相关途径的问题。这项工作的目的是获得关于脂肪细胞去分化的新信息，特别是关于可能参与细胞命运变化的新靶点。为此，从严重肥胖受试者中取样的网膜和皮下成熟脂肪细胞已通过天花板培养去分化。利用沿去分化过程沿着具有不同时间点的实验设计来更好地理解该过程。研究细胞大小、基因和蛋白表达以及细胞因子分泌。IL-6、IL-8、SerpinE 1和VEGF的分泌在去分化过程中增加，而MIF-1的分泌短暂增加。在该过程的早期检测到成熟脂肪细胞转录物（PPARγ2、C/EBPα、LPL和脂联素）的表达显著降低。此外，一些基质重塑转录物（FAP、DPP 4、MMP 1和TGFβ1）快速且强烈地上调。FAP和DPP 4蛋白同时诱导成熟脂肪细胞去分化，支持这些酶在脂肪组织重塑和细胞可塑性中的潜在作用。
Mature adipocytes can reverse their phenotype to become fibroblast-like cells. This is achieved by ceiling culture and the resulting cells, called dedifferentiated fat (DFAT) cells, are multipotent. Beyond the potential value of these cells for regenerative medicine, the dedifferentiation process itself raises many questions about cellular plasticity and the pathways implicated in cell behavior. This work has been performed with the objective of obtaining new information on adipocyte dedifferentiation, especially pertaining to new targets that may be involved in cellular fate changes. To do so, omental and subcutaneous mature adipocytes sampled from severely obese subjects have been dedifferentiated by ceiling culture. An experimental design with various time points along the dedifferentiation process has been utilized to better understand this process. Cell size, gene and protein expression as well as cytokine secretion were investigated. Il-6, IL-8, SerpinE1 and VEGF secretion were increased during dedifferentiation, whereas MIF-1 secretion was transiently increased. A marked decrease in expression of mature adipocyte transcripts (PPARγ2, C/EBPα, LPL and Adiponectin) was detected early in the process. In addition, some matrix remodeling transcripts (FAP, DPP4, MMP1 and TGFβ1) were rapidly and strongly up-regulated. FAP and DPP4 proteins were simultaneously induced in dedifferentiating mature adipocytes supporting a potential role for these enzymes in adipose tissue remodeling and cell plasticity.
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影响因子：
4.3
作者：
Cinti S
通讯作者：
Cinti S
成纤维细胞激活蛋白调节肿瘤相关成纤维细胞和上皮性卵巢癌细胞
影响因子：
5.2
作者：
Lai, Dongmei;Ma, Li;Wang, Fangyuan
通讯作者：
Wang, Fangyuan
影响因子：
5.8
作者：
Blouin, K;Richard, C;Tchernof, A
通讯作者：
Tchernof, A
影响因子：
4.3
作者：
Balaziova, Eva;Busek, Petr;Sedo, Aleksi
通讯作者：
Sedo, Aleksi
影响因子：
2.8
作者：
Gao, Qian;Zhao, Lili;Yang, Gongshe
通讯作者：
Yang, Gongshe