BMP-11/GDF-11  (骨形态发生蛋白 11)

骨形态发生蛋白 11 (BMP-11; GDF11)，又称生长/分化因子 11，是一种多效配体蛋白，属于 TGFβ 家族。骨形态发生蛋白 11 信号通过激活素受体 II 型、ACVR2A 和 ACVR2B，以及激活素受体 I 型、ACVR1B、ACVR1C 和 TGFBR1，导致 SMAD2 和 SMAD3 磷酸化^[1]。骨形态发生蛋白 11 与生长/分化因子 8 (GDF8) 高度相似，与 GDF8 相比，骨形态发生蛋白 11 表现出更强的 SMAD2/3 激活作用，并通过 I 型激活素样受体激酶受体 ALK4/5/7 发出更有效的信号。此外，骨形态发生蛋白 11 的信号传导受细胞外蛋白拮抗剂控制，包括 FS、FSTL3、GASP1 和 GASP2^[1]。骨形态发生蛋白 11 在发育过程中起着关键作用，包括前/后模式、肾脏、胃、脾脏和内分泌胰腺的形成。在胚胎中，骨形态发生蛋白 11 在腭上皮中也有较强的表达，包括腭架的内侧边缘上皮和中线上皮缝。在整个腭架和舌间质也可见到较不明显的表达^[2]。骨形态发生蛋白 11 最近被发现表达于成人中枢神经系统 (CNS)^[2]，是中枢神经系统形成和命运的重要调节因子^[3]。在老年大脑中，外源性外周传递的骨形态发生蛋白 11 可能增强神经发生和血管生成，并改善神经病理结果。外源增加循环骨形态发生蛋白 11 浓度可能是改善大脑衰老和神经病理的有害方面的可行方法^[3]。

Bone Morphogenetic Protein 11 (BMP-11; GDF11), also known as growth/differentiation factor 11, is a ligand protein with pleiotropic, belongs to TGFβ family. GDF-11/BMP-11 signals through activin receptors type II, ACVR2A and ACVR2B, and activin receptors type I, ACVR1B, ACVR1C and TGFBR1 leading to the phosphorylation of SMAD2 and SMAD3^[1]. GDF-11/BMP-11 is highly similar with growth/differentiation factor 8 (GDF8), and exhibits more potent activator of SMAD2/3 and signals more effectively through the type I activin-like receptor kinase receptors ALK4/5/7 than GDF8. Furthermore, signaling by GDF-11/BMP-11 is controlled by extracellular protein antagonists, including FS, FSTL3, GASP1, and GASP2^[1]. GDF-11/BMP-11 plays pivotal roles during development, including anterior/posterior patterning, formation of the kidney, stomach, spleen and endocrine pancreas. In the embryo, GDF-11/BMP-11 also shows strong expression is seen in the palatal epithelia, including the medial edge epithelial and midline epithelial seam of the palatal shelves. Less pronounced expression is also seen throughout the palatal shelf and tongue mesenchyme^[2]. GDF-11/BMP-11 is lately found expressing in the adult central nervous system (CNS)^[2], is an important regulator of CNS formation and fate^[3]. In the aged brain, exogenous, peripherally delivered GDF-11/BMP-11 may enhance neurogenesis and angiogenesis, as well as improve neuropathological outcomes. Exogenously increasing circulating GDF-11/BMP-11 concentrations may be a viable approach for improving deleterious aspects of brain aging and neuropathology^[3].

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