Yang Hongguo, Qin Xiaodan, Guo Yuanyuan, Tao Cuicui, Cao Jun, Cheng Tingcai, Liu Chun
State Key Laboratory of Resource Insects, Southwest University, Chongqing 400715, China.
State Key Laboratory of Resource Insects, Southwest University, Chongqing 400715, China.
Int J Biol Macromol. 2025 May;308(Pt 3):142335. doi: 10.1016/j.ijbiomac.2025.142335. Epub 2025 Mar 26.
Silk protein produced by the silk gland of silkworm (Bombyx mori), finds extensive application in tissue engineering and biomedicine. Elucidating the molecular mechanisms governing silk gland development is critical for optimizing silk protein production and its biomedical applications. Prior studies demonstrated that Bmgsb influences cell fate determination through modulation of endoreplication. To further investigate the molecular mechanism of Bmgsb, transcriptome analysis identified a novel gene, designated Bmubxn-4. Dual-luciferase reporter and electrophoretic mobility shift assays (EMSA) demonstrated that Bmgsb directly regulates Bmubxn-4 transcription. Bmubxn-4 knockdown in the ASG resulted in increased cell size, DNA endoreplication and upregulation of cell cycle-related genes. Bmubxn-4 knockdown in the AMSG resulted in developmental defects and upregulation of ubiquitin-proteasome system (UPS)-related genes. These findings indicate that Bmubxn-4, a direct target gene of Bmgsb, plays a crucial role in silk gland cell redifferentiation and DNA endoreplication. This study provides novel insights into silk gland cell differentiation and the transcriptional regulation of silk protein.
家蚕（Bombyx mori）丝腺产生的丝蛋白在组织工程和生物医学中有着广泛应用。阐明调控丝腺发育的分子机制对于优化丝蛋白生产及其生物医学应用至关重要。先前的研究表明，Bmgsb通过调节核内复制来影响细胞命运决定。为了进一步研究Bmgsb的分子机制，转录组分析鉴定出一个新基因，命名为Bmubxn - 4。双荧光素酶报告基因和电泳迁移率变动分析（EMSA）表明，Bmgsb直接调控Bmubxn - 4的转录。在后部丝腺中敲低Bmubxn - 4导致细胞大小增加、DNA核内复制以及细胞周期相关基因上调。在中部丝腺中敲低Bmubxn - 4导致发育缺陷以及泛素 - 蛋白酶体系统（UPS）相关基因上调。这些发现表明，Bmubxn - 4作为Bmgsb的直接靶基因，在丝腺细胞再分化和DNA核内复制中起关键作用。本研究为丝腺细胞分化和丝蛋白的转录调控提供了新见解。
