MicroRNA-143 inhibits proliferation and promotes apoptosis of thymocyte by targeting CXCL13 in myasthenia gravis mice models

Dong-Mei Wu, Xin Wen, Xin-Rui Han, Shan Wang, Yong-Jian Wang, Min Shen, Shao-Hua Fan, Juan Zhuang, Zi-Feng Zhang, Qun Shan, Meng-Qiu Li, Bin Hu (+3 others)
2018 American Journal of Physiology - Cell Physiology  
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder, affecting the quality of life of millions of people worldwide. The current study aims to determine the relationship between microRNA-143 (miR-143) and CXCL13, and whether it influences the pathogenesis of myasthenia gravis (MG). Thymus specimens were resected from patients with thymic hyperplasia combined MG, and then infused into normal mouse cavities to establish MG mice models. Immunohistochemistry, RT-qPCR, in situ
more » ... n situ hybridization detection, and Western blot analysis were employed to identify the expression of miR-143 and CXCL13 in MG and normal mice. The obtained thymocytes were cultured in vitro and transfected with a series of miR-143 mimic, miR-143 inhibitor, oe-CXCL13 or siRNA against CXCL13. MTT and flow cytometry assays were employed to assess cell viability, cycle entry, and apoptosis of the thymocytes. Dual luciferase reporter assay provided verification, confirming CXCL13 was the target gene of miR-143. Low miR-143 expression in the thymus tissues of the MG mice was detected, which presented with a reciprocal relationship with the expression rate of CLCX13. Observations in relation to the interactions between miR-143 mimic or siRNA CXCL13 exposure resulted in reduced cell viability, with a greater number of cells arrested at the G0/G1 phase, and a greater rate of induced apoptosis. Furthermore, overexpression of CXCL13 rescued miR-143 mimic-induced apoptosis. The findings have identified the potential role of miR-143 as a MG development mediator by targeting CXCL13. The key results obtained provide a promising experimental basis for the targeted intervention treatment of miR-143.
doi:10.1152/ajpcell.00090.2018 pmid:30404560 fatcat:thtpvkm3lzb2ddqu6wfrjyzcyy