滋养层
生物
细胞生物学
HMGB1
胎盘
自噬
MAPK/ERK通路
胚胎干细胞
信号转导
胎盘形成
自噬体
胎儿
免疫学
遗传学
怀孕
细胞凋亡
基因
炎症
作者
Mingrui Li,Enxiang Chen,Zhuo‐Hang Li,Hong-Lan Song,Yi Zhang,Fangfang Li,You-Long Xie,Jing Tang,Yubin Ding,Lijuan Fu
标识
DOI:10.1093/biolre/ioae064
摘要
Abstract Objective The purpose of this study is to investigate the role of high mobility group protein B1 (HMGB1) in placental development and fetal growth. Methods We employed the Cre-loxP recombination system to establish a placenta-specific HMGB1 knockout mouse model. Breeding HMGB1flox/flox mice with Elf5-Cre mice facilitated the knockout, leveraging Elf5 expression in extra-embryonic ectoderm, ectoplacental cone, and trophoblast giant cells at 12.5 days of embryonic development. The primary goal of this model was to elucidate the molecular mechanism of HMGB1 in placental development, assessing parameters such as placental weight, fetal weight, and bone development. Additionally, we utilized lentiviral interference and overexpression of HMGB1 in human trophoblast cells to further investigate HMGB1’s functional role. Results Our findings indicate that HMGB1flox/floxElf5cre/+ mouse display fetal growth restriction (FGR), characterized by decreased placental and fetal weight and impaired bone development. And the absence of HMGB1 inhibits autophagosome formation, impairs lysosomal degradation, and disrupts autophagic flux. Depletion of HMGB1 in human trophoblast cells also suppresses cell viability, proliferation, migration, and invasion by inhibiting the ERK signaling pathway. Overexpression of HMGB1 observed the opposite phenotypes. Conclusions HMGB1 participates in the regulation of autophagy through the ERK signaling pathway and affects placental development.
科研通智能强力驱动
Strongly Powered by AbleSci AI