title: MicroRNA-155 regulates T cell proliferation through targeting GSK3β in cardiac allograft rejection in a murine transplantation model.
abstract: Here we investigated the activity and regulation of miR-155 during cardiac allograft rejection (AR), and to examine the feasibility of using miR-155 as a biomarker of graft status. Expression of miR-155 in graft-infiltrating lymphocytes (GIL), T cells isolated from spleen (TFS), and lymphocytes separated from blood (LFB) was significantly increased during cardiac AR while GSK3β was downregulated in GIL and TFS. Inhibition of miR-155 impaired lymphocyte proliferation and enhanced the expression of GSK3β. Moreover, pharmacological inactivation of GSK3β resulted in rescue of the proliferative capability of T cells pretreated with a miR-155 inhibitor. Luciferase reporter assay confirmed that miR-155 interacted with the 3'-untranslated region (UTR) of GSK3β directly. In particular, the miR-155 in LFB can distinguish recipients with AR from syngeneic controls from POD 3 and later. The present study provides a better understanding of the pathophysiological process underlying cardiac AR progression.
authors: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University, School of Medicine, 1678 Dongfang Road, Pudong, Shanghai 200127, China.
authors: Zhiyu
authors: Z
authors: Feng
authors: Yu
authors: Y
authors: Xia
authors: Mingjie
authors: M
authors: Zhang
authors: Jinghao
authors: J
authors: Zheng
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D049109:Cell Proliferation; D015536:Down-Regulation; D020869:Gene Expression Profiling; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006084:Graft Rejection / Q000235:genetics*; D057809:HEK293 Cells; D016027:Heart Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*; D014184:Transplantation, Homologous
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3