4.6 Article

Smad4 mediates Bmf involvement in sheep granulosa cell apoptosis

Journal

GENE
Volume 817, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.gene.2022.146231

Keywords

Bmf; Cell apoptosis; Granulosa cells; Sheep; Smad4

Funding

  1. National Natural Science Foundation of China [31960664]
  2. Gansu Agricultural University Scientific research start-up funds for openly-recruited doctors [2017RCZX-17]

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The study demonstrates the significant roles of Bmf and Smad4 in the apoptosis of sheep granulosa cells (GCs), shedding light on the regulatory pathway between Smad4 and Bmf.
Bcl-2-modifying factor (Bmf) functions to mediate follicular atresia and oocyte growth in mice. It has been proven that TGF-beta can induce Bmf expression via the Smad4 pathway in a variety of cells, and then induce cell apoptosis. Based on this, we hypothesized that Smad4 and Bmf may play important roles in the apoptosis of granulosa cells (GCs) in domestic animals. This study used small-tailed Han sheep follicular GCs cultured in vitro as a model system, and overexpression or interference experiments, to explore the biological roles of Bmf and reveal the preliminary regulatory mechanisms between Smad4 and Bmf in the process of GCs' apoptosis. We found that the proliferation rate of sheep GCs was significantly increased after the knockdown of Bmf, whereas overexpressing Bmf increased the apoptosis rate of GCs, results also verified by the expression patterns of PCNA, Bcl-2, and Bax genes. After the Smad4 knockdown, the apoptosis rate of GCs was increased, while the mRNA and protein expression of Bmf was significantly up-regulated. A rescue experiment verified that the Bmf knockdown could alleviate GCs' apoptosis induced by Smad4 knockdown. In conclusion, our study not only elucidated an important role for Bmf in the apoptosis of sheep GCs but also revealed a new regulatory pathway between Smad4 and Bmf in this process.

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