Mathew A, Trausch-Azar J S, Azar C, Schuetz M, Mahjoub M R, Schwartz A L
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Medicine (Nephrology), Washington University School of Medicine, St. Louis, Missouri, USA.
Physiol Rep. 2025 May;13(10):e70383. doi: 10.14814/phy2.70383.
While cellular proteins exist in a dynamic state maintained by the balance of synthesis and degradation, there is a paucity of information on these processes in placental trophoblasts, including within cytotrophoblasts which differentiate into multi-nucleate syncytiotrophoblasts. TFEB, a transcription factor with a myriad of cellular activities, is one of the most abundant genes expressed in syncytiotrophoblasts compared to cytotrophoblasts. TFEB is localized to the nucleus of human BeWo differentiated syncytiotrophoblasts and to the cytoplasm of the undifferentiated cytotrophoblasts. Within both the cytotrophoblasts and syncytiotrophoblasts, TFEB exists in subcellular compartments as both phosphorylated and unphosphorylated forms and translocates between cytoplasm and nucleus upon amino acid starvation/refeeding. Endogenous TFEB and endogenous phospho-TFEB are both rapidly (t ~ 2-3 h) degraded via the ubiquitin proteasome system in cytotrophoblasts and in syncytiotrophoblasts. These results suggest dynamic regulatory processes during trophoblast development/differentiation.
虽然细胞蛋白质以合成与降解平衡所维持的动态状态存在，但关于胎盘滋养层细胞中这些过程的信息却很匮乏，包括在分化为多核合体滋养层细胞的细胞滋养层细胞内。转录因子EB（TFEB）具有多种细胞活性，与细胞滋养层细胞相比，它是合体滋养层细胞中表达最丰富的基因之一。TFEB定位于人BeWo分化的合体滋养层细胞的细胞核以及未分化的细胞滋养层细胞的细胞质中。在细胞滋养层细胞和合体滋养层细胞内，TFEB以磷酸化和非磷酸化形式存在于亚细胞区室中，并在氨基酸饥饿/再投喂时在细胞质和细胞核之间转运。内源性TFEB和内源性磷酸化TFEB在细胞滋养层细胞和合体滋养层细胞中均通过泛素蛋白酶体系统迅速（t约2 - 3小时）降解。这些结果表明滋养层细胞发育/分化过程中的动态调节过程。
