Stomatin-like protein 2 (SLP2) regulates the proliferation and invasion of trophoblast cells by modulating mitochondrial functions

• Published in: Placenta (Eastbourne) Vol. 100; pp. 13 - 23
• Main Authors: Zhang, Xue, Li, Bing-Yi, Fu, Li-Juan, Adu-Gyamfi, Enoch Appiah, Xu, Bai-Ruo, Liu, Tai-Hang, Chen, Xue-Mei, Lan, Xi, Wang, Ying-Xiong, Xu, Hong-Bing, Ding, Yu-Bin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.10.2020
• Subjects: invasion; migration; miscarriage; mitochondria; Proliferation; SLP2; migration; Proliferation; invasion; miscarriage; SLP2; mitochondria
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2020.07.008

Stomatin-like protein 2 (SLP2) is highly expressed in human first trimester trophoblast cells, but its functions in placental morpho-physiology remain unknown. This study aimed to determine the role of SLP2 in the proliferation and invasion of human first trimester trophoblast cells. Immunofluorescence was used to determine the expression and localization of SLP2 in normal and miscarriage human first trimester placenta. Western blot was used to determine the expression of SLP2, PCNA, Cyclin D3, N-cadherin, Vimentin, PGC1α and PPARα in HTR-8/SVneo cells. SLP2 was knocked down in the HTR-8/SVneo cells by using si-Slp2. Wound healing and migration assays were used to determine the effect of SLP2 knockdown on the migration and invasion in the HTR-8/SVneo cells. Mitochondrial membrane potential, reactive oxygen species (ROS), ATP production and biogenesis were measured to assess the effects of SLP2 knockdown on mitochondrial functions. SLP2 was strongly expressed in the cytotrophoblasts (CTB), syncytiotrophoblast (STB) and extravillous trophoblasts (EVT) of normal pregnancy placenta as compared to miscarriage placenta. SLP2 was highly expressed in the invasive EVT cell lines, HTR-8/SVneo and HPT-8 compared to the CTB cell line JAR. Knockdown of SLP2 significantly inhibited the migration and invasion of HTR-8/SVneo cells and placental villous explants, and repressed mitochondrial biogenesis and functions in HTR-8/SVneo cells. Silencing of SLP2 inhibited the proliferation, migration and invasion of HTR-8/SVneo cells via the impairment of mitochondrial functions. This indicates that the downregulation of SLP2 in miscarriage placenta could be part of the pathogenesis and pathophysiology of the disease. •SLP2 is expressed in the CTB, STB and EVT of human first trimester placenta.•Knockdown of SLP2 inhibited proliferation, invasion and migration of HTR8/SVneo cells.•Knockdown of SLP2 resulted in mitochondrial dysfunctions.•SLP2 expression was downregulated in the miscarriage placental villi.