BMP-8a  (骨形态发生蛋白 8a)

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%。BMP8A 基因编码TGF-β超家族蛋白的分泌配体，结合各种 TGF-β 受体，导致 SMAD 家族转录因子的招募和激活，并调节基因表达。所编码的前原蛋白被蛋白水解处理以生成二硫连接的同型二聚体的单个亚基^[2]。骨形态发生蛋白 BMP-8a 由生长中的卵泡内的颗粒细胞分泌，并激活颗粒细胞中的 SMAD1/5/8 和 SMAD2/3 通路，抑制促性腺激素诱导的孕酮产生和激素生成相关基因的表达^[1]。骨形态发生蛋白 BMP-8a 还通过激活精原细胞中的 SMAD1/5/9 和 SMAD2/3 来维持精子发生，从而在生殖系统的发育中发挥作用。骨形态发生蛋白 BMP-8a 也在透明细胞肾细胞癌 (ccRCC) 中激活 Nrf2 和 Wnt 通路，促进癌细胞增殖和抑制细胞凋亡^[2]。

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 BMP8A, which is mainly secreted by granulosa cells within growing ovarian follicles. BMP8A encodes a secreted ligand of the TGF-β superfamily of proteins to bind various TGF-beta receptors, leading to recruitment and activation of SMAD family transcription factors and regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer^[2]. BMP-8A protein activates the SMAD1/5/8 and the SMAD2/3 pathways in granulosa cells, to inhibit gonadotropin-induced progesterone production and steroidogenesis-related gene expression^[1]. BMP8A protein plays a role in development of the reproductive system by sustaining spermatogenesis by activating both SMAD1/5/9 and SMAD2/3 in spermatogonia. BMP-8A protein also activates Nrf2 and Wnt pathways in clear cell renal cell carcinoma (ccRCC) to promote cell proliferation and inhibit apoptosis^[2].

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