Effect of hydroxychloroquine and chloroquine on syncytial differentiation and autophagy in primary human trophoblasts

Biomedicine & Pharmacotherapy

卷:149

Jae Ryoung Hwang¹  Nagyeong Byun²  Minji Choi³  Soo-young Oh⁴  Jung-Sun Kim⁴  Suk-Joo Choi⁴  Cheong-Rae Roh⁵  Yun-Sun Choi⁶  Ji-Hee Sung⁷ 

[1] Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;

[2] Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea;

[3] Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea;

[4] Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;

[5] Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea;

关键词: Trophoblast;    Differentiation;    Syncytiotrophoblasts;    Autophagy;    Hydroxychloroquine;    Chloroquine;   

DOI  :  

来源: DOAJ

【 摘 要 】

During placentation, cytotrophoblasts differentiate and fuse to form multinucleated cells (syncytiotrophoblasts) in a process that involves autophagy. Appropriate syncytial differentiation is essential for establishing a healthy pregnancy. In this study, we evaluated the effect of two chloroquine compounds, hydroxychloroquine (HCQ) and chloroquine (CQ), on syncytial differentiation and autophagy in cultured primary human trophoblasts (PHTs). PHT cells were isolated from the human term placenta. Bafilomycin, a well-known autophagy inhibitor, was used as a positive control. Biochemical and morphological differentiation was assessed in syncytiotrophoblasts, and autophagy-related proteins and genes were evaluated. Affymetrix Human Gene 2.0 ST Array profiling was used to identify genes affected by HCQ during syncytial differentiation. Chloroquine compounds lowered the production of beta-human chorionic gonadotropin (β-hCG) and the fusion index in PHTs. Syncytial differentiation in PHT was associated with the increased expression of ATG4C mRNA (autophagy-related gene), and this expression was affected by CQ but not by HCQ. Microarray analysis revealed that HCQ or CQ affected several genes (MMP15, GPC3, CXCL10, TET-1, and S100A7) during syncytial differentiation, which were different from that of the syncytial differentiation suppression (Ham’s/Waymouth media) or autophagy inhibition (bafilomycin treatment). Using Kyoto Encyclopedia of Genes and Genomes analysis we identified that HCQ might affect JAK2 signaling in the syncytial differentiation of PHT. In conclusion, chloroquine compounds could mitigate biochemical and morphological syncytial trophoblast differentiation in cultured PHT cells through the JAK signaling pathway rather than the inhibition of autophagic activity.

【 授权许可】

Unknown