Setiawan Abdul Malik, Kamarudin Taty Anna, Abd Ghafar Norzana
Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Department of Anatomy, Maulana Malik Ibrahim State Islamic University, Malang, Indonesia.
Front Cell Dev Biol. 2022 Oct 21;10:1045103. doi: 10.3389/fcell.2022.1045103. eCollection 2022.
Bone morphogenetic protein 4 (BMP4) is a member of the transforming growth factor beta (TGF-β) superfamily of cytokines responsible for stem cells' commitment to differentiation, proliferation, and maturation. To date, various studies have utilized BMP4 as a chemical inducer for differentiation of human mesenchymal stem cells (MSCs) based on its potential. BMP4 drives differentiation of ADSC TGF-β signaling pathway by interactions with BMP receptors leading to the activation of smad-dependent and smad-independent pathways. The BMP4 signaling pathways are regulated by intracellular and extracellular BMP4 antagonists. Extracellular BMP4 antagonist prevents interaction between BMP4 ligand to its receptors, while intracellular BMP4 antagonist shutdowns the smad-dependent pathways through multiple mechanisms. BMP4 proved as one of the popular differentiation factors to induce ADSC differentiation into cell from mesodermal origin. However, addition of all-trans retinoic acid is also needed in trans-differentiation of ADSC into ectodermal lineage cells. Suggesting that both BMP4 and RA signaling pathways may be necessary to be activated for trans-differentiation of ADSC.
骨形态发生蛋白4(BMP4)是转化生长因子β(TGF-β)细胞因子超家族的成员,负责干细胞的分化、增殖和成熟。迄今为止,基于其潜力,各种研究已将BMP4用作人骨髓间充质干细胞(MSCs)分化的化学诱导剂。BMP4通过与BMP受体相互作用驱动脂肪干细胞(ADSC)的分化,激活TGF-β信号通路,从而导致smad依赖性和smad非依赖性途径的激活。BMP4信号通路受细胞内和细胞外BMP4拮抗剂的调节。细胞外BMP4拮抗剂可阻止BMP4配体与其受体之间的相互作用,而细胞内BMP4拮抗剂则通过多种机制关闭smad依赖性途径。BMP4被证明是诱导ADSC分化为中胚层来源细胞的常用分化因子之一。然而,在将ADSC转分化为外胚层谱系细胞的过程中,还需要添加全反式维甲酸。这表明,BMP4和视黄酸(RA)信号通路可能都需要被激活才能实现ADSC的转分化。
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