BMP-8a

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].