2. Academic Validation
  3. HMGB1 regulates autophagy of placental trophoblast through ERK signaling pathway

HMGB1 regulates autophagy of placental trophoblast through ERK signaling pathway

  • Biol Reprod. 2024 Apr 22:ioae064. doi: 10.1093/biolre/ioae064.
Ming-Rui Li 1 2,  En-Xiang Chen 3,  Zhuo-Hang Li 2,  Hong-Lan Song 1,  Yi Zhang 2,  Fang-Fang Li 2,  You-Long Xie 2,  Jing Tang 3,  Yu-Bin Ding 1 2,  Li-Juan Fu 4 5
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Chongqing 400013, China.
  • 2 Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing 400016, China.
  • 3 School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400042, China.
  • 4 Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, School of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.
  • 5 Department of Basic Medical Sciences, Changsha Medical University, Hunan 410219, China.
PMID: 38647664 DOI: 10.1093/biolre/ioae064
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.

Keywords

Autophagy; Fetal growth restriction; High mobility group protein B1; Placenta; Trophoblast.

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