BMP-8b  (骨形态发生蛋白 8b)

BMP-8 是一种多效配体蛋白，具有生殖系统调节作用。BMP-8由一对 BMP8A 和 BMP8B 编码，属于 TNF-β 家族，BMP-8通过与I型受体BMPR1A和II型受体BMPR2结合，启动典型的BMP信号级联。骨形态发生蛋白 BMP 8a 和 BMP 8b 都在卵巢中富集，并激活不同细胞中的经典 BMP 信号，包括精原细胞、P19 和 293T 细胞^[1]。BMP-8 广泛存在于不同动物体内，骨形态发生蛋白 BMP 8a 和 BMP 8b 在人体内的序列与小鼠有很大差异，相似度分别为 85.96% 和 74.44%。骨形态发生蛋白 BMP 8b 则由棕色/米色脂肪细胞分泌，能够增强能量耗散，在脂肪组织 (adipose tissue) 中作为神经-血管重塑的互联调节因子，是肥胖研究的潜在靶点^[2]。骨形态发生蛋白 BMP 8b 通过中枢和外周作用增加棕色脂肪组织的产热。因此，骨形态发生蛋白 BMP 8b 有助于肾上腺素能诱导的脂肪组织神经血管网络重构，并通过脂肪细胞：1) 分泌神经调节素-4 (NRG4)，促进体外交感神经轴突生长和分支；2) 诱导促血管生成的转录和分泌谱，促进血管发芽^[2]。骨形态发生蛋白 BMP 8b 还参与 caspase-3 和 9 的激活，以及凋亡抑制胰腺癌细胞生长^[4]。

BMP-8 is a pleiotropic ligand protein act as a reproductive system regulator. BMP-8 is encoded by a pair of genes, BMP8A and BMP8B, belonging to TNF-β family. GMP-8 initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2. Both BMP8A and BMP8B are enriched in the ovary and activate canonical BMP signaling in different cells, including spermatogonia, P19 and 293T cells^[1]. BMP-8 is widely found in different animals, while the sequences of BMP-8A and BMP-8B in human are highly different from Mouse with similarities of 85.96% and 74.44%, respectively. As for BMP8B, which protein is secreted by brown/beige adipocytes and enhances energy dissipation, serves as an interconnected regulator of neuro-vascular remodeling in AT and is potential targets in obesity^[2]. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions^[3]. Thus BMP8B contributes to adrenergic-induced remodeling of the neuro-vascular network in adipose tissue, therefore through the adipocytes to 1) secrete neuregulin-4 (NRG4), which promotes sympathetic axon growth and branching in vitro, and 2) induce a pro-angiogenic transcriptional and secretory profile that promotes vascular sprouting^[2]. BMP8B also involve in activation of caspase-3 and -9, and apoptosis to inhibit pancreatic cancer cell growth^[4].

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