College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Xueshi Road, Hangzhou 310006, China.
Int J Mol Sci. 2021 Dec 24;23(1):199. doi: 10.3390/ijms23010199.
Decidualization is essential to the establishment of pregnancy in rodents and primates. Laminin A5 (encoding by ) is a member of the laminin family, which is mainly expressed in the basement membranes. Although laminins regulate cellular phenotype maintenance, adhesion, migration, growth, and differentiation, the expression, function, and regulation of laminin A5 during early pregnancy are still unknown. Therefore, we investigated the expression and role of laminin A5 during mouse and human decidualization. Laminin A5 is highly expressed in mouse decidua and artificially induced deciduoma. Laminin A5 is significantly increased under in vitro decidualization. Laminin A5 knockdown significantly inhibits the expression of , a marker for mouse decidualization. Progesterone stimulates the expression of laminin A5 in ovariectomized mouse uterus and cultured mouse stromal cells. We also show that progesterone regulates laminin A5 through the PKA-CREB-C/EBPβ pathway. Laminin A5 is also highly expressed in human pregnant decidua and cultured human endometrial stromal cells during in vitro decidualization. Laminin A5 knockdown by siRNA inhibits human in vitro decidualization. Collectively, our study reveals that laminin A5 may play a pivotal role during mouse and human decidualization via the PKA-CREB-C/EBPβ pathway.
蜕膜化对于啮齿动物和灵长类动物的妊娠建立至关重要。层粘连蛋白 A5(由 编码)是层粘连蛋白家族的成员,主要表达于基底膜。尽管层粘连蛋白调节细胞表型维持、黏附、迁移、生长和分化,但层粘连蛋白 A5 在早孕期间的表达、功能和调节仍不清楚。因此,我们研究了层粘连蛋白 A5 在小鼠和人蜕膜化过程中的表达和作用。层粘连蛋白 A5 在小鼠蜕膜和人工诱导的蜕膜瘤中高度表达。体外蜕膜化时层粘连蛋白 A5 显著增加。层粘连蛋白 A5 敲低显著抑制了小鼠蜕膜化的标志 的表达。孕酮刺激去卵巢小鼠子宫和培养的小鼠基质细胞中层粘连蛋白 A5 的表达。我们还表明,孕酮通过 PKA-CREB-C/EBPβ 通路调节层粘连蛋白 A5。层粘连蛋白 A5 在人妊娠蜕膜和体外培养的人子宫内膜基质细胞中也高度表达。siRNA 介导的层粘连蛋白 A5 敲低抑制了人体外蜕膜化。综上所述,我们的研究表明,层粘连蛋白 A5 可能通过 PKA-CREB-C/EBPβ 通路在小鼠和人蜕膜化过程中发挥关键作用。