BMP-7  (骨形态发生蛋白 7)

骨形态发生蛋白 7 (BMP-7) 是一种多效性配体蛋白，属于 TGFβ 家族。BMP-7 参与调节癌细胞的增殖、侵袭和迁移，与多种人类肿瘤相关^[1]。BMP-7 似乎也表现出对血管的抗炎作用，并可能发挥维持血管完整性的功能^[2]。BMP-7 可减弱血管钙化，但也可纠正尿毒症相关的高磷血症，并刺激原位磷酸骨化沉积，同时通过直接作用于血管平滑肌细胞防止血管钙化^[3]。BMP/TGFβ 信号通路参与血管和瓣膜稳态，这是胚胎发育的关键过程^[4]。由于血清、血小板衍生生长因子亚单位 BB (PDGF-BB) 或 TGFβ1 的刺激，BMP-7 还抑制原发性人主动脉平滑肌细胞 (SMCs) 的增殖，并维持血管 SMC 表型的表达^[2]。BMP-7 结合 ALK2 或 ACVR2A/BMPR2 激发信号，该信号可通过抑制 SMADs (包括 SMAD6 和 SMAD7) 终止，SMAD6 和 SMAD7 被 BMP 信号激活和诱导，并通过多种机制关闭 BMP 信号^[5]。而 BMP-7 基因敲低导致 p-Smad1/5/9 表达明显降低，BMP-7-Smad1/5/9 信号通路活性降低，上皮-间质转化 (EMT) 过程逆转^[1]。在肺癌中，BMP-7 抑制骨转移，诱导细胞凋亡和细胞周期阻滞。在恶性黑色素瘤中，BMP-7 可诱导间充质上皮转化，抑制癌细胞转移。BMP-7 抑制 EMT 相关基因和细胞侵袭，抑制端粒酶，缩短端粒，诱导乳腺癌细胞衰老和凋亡。在骨转移性乳腺癌和前列腺癌模型中，BMP-7 能增加细胞增殖和迁移^[1]。BMP-7 广泛存在于不同的动物中，而人源的序列与大鼠和小鼠高度相似，序列相似度分别为 98.08% 和 97.67%。

Bone Morphogenetic Protein 7 (BMP-7) is a ligand protein with pleiotropic, belongs to TGFβ family. BMP-7 is involved in regulating the proliferation, invasion and migration of cancer cells, associated with a variety of human tumors^[1]. BMP-7 also appears to exhibit anti-inflammatory effects on the vasculature, and may function to maintain vascular integrity^[2]. BMP-7 attenuates vascular calcification, but also corrects hyperphosphatemia associated with uremia, and stimulates orthotopic skeletal phosphate deposition while simultaneously preventing vascular calcification by direct action on vascular smooth muscle cells^[3]. BMP/TGFβ signaling to involve in vascular and valvular homeostasis, which is a critical process of embryonic development^[4]. BMP-7 inhibits primary human aortic smooth muscle cells (SMCs) proliferation due to stimulation with serum, platelet-derived growth factor subunit BB (PDGF-BB) or TGFβ1, and maintains the expression of the vascular SMC phenotype^[2]. BMP-7 binds ALK2 or ACVR2A/BMPR2 to signal, and can be terminated by inhibitory SMADs including SMAD6 and SMAD7, which are activated and induced by BMP signaling and switch off BMP signaling via multiple mechanisms^[5]. However, BMP-7 knockdown results the expression of p-Smad1/5/9 significantly decreased, accompanied with BMP-7-Smad1/5/9 signaling pathway inactive and epithelial-mesenchymal transition (EMT) process reverse^[1]. In lung cancer, BMP-7 inhibits bone metastasis, and induces apoptosis and cell cycle arrest. In malignant melanoma, BMP-7 can induce mesenchymal-epithelial transformation and inhibit the metastasis of cancer cells. BMP-7 inhibit epithelial-mesenchymal transition (EMT)-related genes and cell invasion, inhibit telomerase, shorten telomeres, and induce the aging and apoptosis of breast cancer cells. BMP-7 increases the cell proliferation and migration potential in a model of metastatic breast cancer in the bone and prostate cancer^[1]. BMP-7 is widely found in different animals, while the sequence in human is highly similar to Rat (98.08%), and Mouse (97.67%).

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