HMGB1 regulates autophagy of placental trophoblast through ERK signaling pathway.
Biol Reprod
; 111(2): 414-426, 2024 Aug 15.
Article
in En
| MEDLINE
| ID: mdl-38647664
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 the HMGB1flox/floxElf5cre/+ mouse displays fetal growth restriction, characterized by decreased placental and fetal weight and impaired bone development. 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Placenta
/
Autophagy
/
Trophoblasts
/
MAP Kinase Signaling System
/
HMGB1 Protein
Limits:
Animals
/
Female
/
Humans
/
Male
/
Pregnancy
Language:
En
Journal:
Biol Reprod
Year:
2024
Document type:
Article
Affiliation country:
China