Neuromedin B drives goat granulosa cell proliferation via NMBR-mediated calcium homeostasis

作者：Rongxin Xia, Qi Zhang, Junhui Shao, Yuan Wang, Xinyi Lv, Rui Chen, Zhen Lu, Yanli Zhang, Feng Wang, Guomin Zhang · 发表于：Journal of Ovarian Research · 年份：2025 · DOI：10.1186/s13048-025-01844-7 · 被引用次数：1 · 研究领域：Proteoglycans and glycosaminoglycans research、Neuropeptides and Animal Physiology、Animal health and immunology

BACKGROUND: Neuromedin B (NMB) has been implicated in the regulation of female reproductive functions, yet its precise role and underlying mechanisms in ovarian follicular development remain undefined. Granulosa cells (GCs), the principal functional cells within ovarian follicles, directly govern follicular growth and maturation through their proliferation and differentiation. In this study, we explored the regulatory effects and molecular mechanisms of NMB and its receptor neuromedin B receptor (NMBR) on goat GC proliferation. RESULTS: We documented dynamic expression patterns of NMB and NMBR throughout ovarian and follicular development. Exogenous NMB treatment significantly enhanced GC proliferation, as evidenced by an increased fraction of S-phase cells and upregulation of CCNE1 and CDK1/2/6. Mechanistically, NMB bound to NMBR to activate phospholipase C β1 (PLCβ1), triggering endoplasmic reticulum (ER) Ca²⁺ release and significantly raising cytosolic Ca²⁺ levels while alleviating ER stress. Further analyses revealed that NMB strengthened mitochondria-associated ER membranes (MAMs) formation via the IRE1α–IP3R–VDAC1 axis, facilitating Ca²⁺ transfer into mitochondria. This led to enhanced mitochondrial function, including increased mitochondrial membrane potential, elevated respiratory chain complex activities, augmented ATP production, and promotion of mitochondrial network fusion. Importantly, these effects were abolished by an NMBR antagonist. CONCLUSIONS: The molecular...