Systematic Characterization of Autophagy in Gestational Diabetes Mellitus

• Published in: Endocrinology (Philadelphia) Vol. 158; no. 8; pp. 2522 - 2532
• Main Authors: Ji, Lulu, Chen, Zhiguo, Xu, Yating, Xiong, Guoping, Liu, Rui, Wu, Chao, Hu, Hanyang, Wang, Lin
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.08.2017; Oxford University Press
• 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
• ISSN: 0013-7227; 1945-7170; 1945-7170
• DOI: 10.1210/en.2016-1922

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.