Sulforaphane Promotes Proliferation of Porcine Granulosa Cells via the H3K27ac-Mediated GDF8-ALK5-ERK Pathway,Journal of Agricultural and Food Chemistry

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Sulforaphane Promotes Proliferation of Porcine Granulosa Cells via the H3K27ac-Mediated GDF8-ALK5-ERK Pathway
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-18 , DOI: 10.1021/acs.jafc.4c06178
Jiaqi Zhou ₁ , Chen Fu ₁ , Ming Shen ₁ , Jingli Tao ₁ , Honglin Liu ₁

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Follicle development, a crucial process in reproductive biology, hinges upon the dynamic proliferation of granulosa cells (GCs). Growth differentiation factor-8 (GDF8) is well-known as myostatin for inhibiting skeletal muscle growth, and it also exists in ovarian GCs and follicle fluid. However, the relationship between GCs proliferation and GDF8 remains elusive. Sulforaphane (SFN) is a potent bioactive compound, which in our study has been demonstrated to induce the expression of GDF8 in GCs. Meanwhile, we discover a novel role of SFN in promoting the proliferation of porcine GCs. Specifically, SFN enhances GCs proliferation by accelerating the progression of the cell cycle through the G1 phase to the S phase. By performing gene expression profiling, we showed that the promoting proliferative effects of SFN are highly correlated with the TGF-β signaling pathways and cell cycle. Among the ligand factors of TGF-β signaling, we identify GDF8 as a critical downstream effector of SFN, which acts through ALK5 to mediate SFN-induced proliferation and G1/S transition. In addition, we identify a noncanonical downstream pathway by which GDF8 induces the activation of MAPK/ERK to facilitate the cell cycle progression in GCs. Moreover, we reveal that the expression of GDF8 is regulated by SFN through epigenetic modifications of H3K27 acetylation. These findings not only provide mechanistic insights into the regulation of GCs proliferation but also establish a previously unrecognized role of GDF8 in follicle development, which have significant implications for developing strategies to improve female fertility.

中文翻译：

萝卜硫素通过 H3K27ac 介导的 GDF8-ALK5-ERK 途径促进猪颗粒细胞增殖

卵泡发育是生殖生物学的一个关键过程，取决于颗粒细胞（GC）的动态增殖。生长分化因子-8 (GDF8) 被称为肌肉生长抑制素，可抑制骨骼肌生长，它也存在于卵巢 GC 和卵泡液中。然而，GC 增殖与 GDF8 之间的关系仍不清楚。萝卜硫素 (SFN) 是一种有效的生物活性化合物，我们的研究已证明它可以诱导 GC 中 GDF8 的表达。同时，我们发现SFN在促进猪GC增殖方面具有新的作用。具体来说，SFN 通过加速细胞周期从 G1 期到 S 期的进展来增强 GC 增殖。通过基因表达谱分析，我们发现SFN的促进增殖作用与TGF-β信号通路和细胞周期高度相关。在 TGF-β 信号传导的配体因子中，我们将 GDF8 确定为 SFN 的关键下游效应子，它通过 ALK5 介导 SFN 诱导的增殖和 G1/S 转变。此外，我们还确定了 GDF8 诱导 MAPK/ERK 激活以促进 GC 细胞周期进程的非经典下游途径。此外，我们揭示了 SFN 通过 H3K27 乙酰化的表观遗传修饰来调节 GDF8 的表达。这些发现不仅提供了对GC增殖调节的机制见解，而且还确定了GDF8在卵泡发育中以前未被认识的作用，这对于制定提高女性生育能力的策略具有重要意义。

更新日期：2024-09-19

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