Systematic Characterization of Autophagy in Gestational Diabetes Mellitus

Abstract Autophagy is a dynamic process that degrades and recycles cellular organelles and proteins to maintain cell homeostasis. Alterations in autophagy occur in various diseases; however, the role of autophagy in gestational diabetes mellitus (GDM) is unknown. In the present study, we characteriz...

Full description

Saved in:
Bibliographic Details
Published in:Endocrinology (Philadelphia) 2017-08, Vol.158 (8), p.2522-2532
Main Authors: Ji, Lulu, Chen, Zhiguo, Xu, Yating, Xiong, Guoping, Liu, Rui, Wu, Chao, Hu, Hanyang, Wang, Lin
Format: Article
Language:English
Subjects:
Adult
Apoptosis
Apoptosis - physiology
Autophagy
Autophagy - physiology
Blood Glucose
Cell Line
Circuits
Data analysis
Data processing
Diabetes
Diabetes mellitus
Diabetes, Gestational - physiopathology
Endocrinology
Epigenomics
Female
Gene expression
Gene Expression Regulation
Gene sequencing
Genomes
Genomic analysis
Glucose
Homeostasis
Humans
Hyperglycemia
Organelles
Patients
Phagocytosis
Placenta
Placenta - cytology
Pre-eclampsia
Pregnancy
Proteins
Ribonucleic acid
RNA
RNA-mediated interference
Signaling
Therapeutic targets
Trophoblasts
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Autophagy is a dynamic process that degrades and recycles cellular organelles and proteins to maintain cell homeostasis. Alterations in autophagy occur in various diseases; however, the role of autophagy in gestational diabetes mellitus (GDM) is unknown. In the present study, we characterized the roles and functions of autophagy in GDM patient samples and extravillous trophoblasts cultured with glucose. We found significantly enhanced autophagy in GDM patients. Moreover, high glucose levels enhanced autophagy and cell apoptosis, reducing proliferation and invasion, and these effects were ameliorated through knockdown of ATG5. Genome-wide 5-hydroxymethylcytosine data analysis further revealed the epigenomic regulatory circuitry underlying the induced autophagy and apoptosis in GDM and preeclampsia. Finally, RNA sequencing was performed to identify gene expression changes and critical signaling pathways after silencing of ATG5. Our study has demonstrated the substantial functions of autophagy in GDM and provides potential therapeutic targets for the treatment of GDM patients. Our study as demonstrated enhanced autophagy in the placenta of GDM patients and high glucose-treated extravillous trophoblasts, and these effects were ameliorated through knockdown of ATG5.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2016-1922