Open AccessMesenchymal stem cell transplantation can restore lupus disease-associated miRNA expression and Th1/Th2 ratios in a murine model of SLE
Author(s) -
EungChil Choi,
Minjae Lee,
Ji Woo Song,
Il Seob Shin,
Sung Joo Kim
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep38237
Subject(s) - cyclophosphamide , mesenchymal stem cell , saline , lupus nephritis , transplantation , medicine , microrna , immunology , therapeutic effect , downregulation and upregulation , disease , andrology , cancer research , biology , pathology , chemotherapy , gene , biochemistry
C3.MRL-Fas lpr /J mice spontaneously develop high titers of anti-dsDNA, mild glomerular nephritis, and severe lymphoproliferation symptoms. This study aimed to compare the effects of long-term serial administration of human adipose tissue-derived mesenchymal stem cells (ASCs), and cyclophosphamide treatment in C3.MRL-Fas lpr /J mice using a murine SLE model. C3.MRL-Fas lpr /J mice were divided into saline (C), cyclophosphamide (Y), and ASC (H) treatment groups. Background-matched control C3H mice treated with saline (N) were also compared. The Y group showed the greatest improvement in disease parameters, but with damaged trabecular integrity. ASC transplantation reduced anti-dsDNA levels, glomerular C3 deposition and CD138 proportion significantly, without trabecular damage. Furthermore, both cyclophosphamide and ASC treatment significantly decreased the ratio of Th1/Th2 compared with the saline-treatment. The expression levels of miR-31-5p, miR-96-5p, miR-182-5p, miR-183-5p, and miR-379-5p were significantly higher, while those of miR150-5p were significantly lower in the C group than in the N group. The expression levels of miR-96-5p, miR-182-5p in the Y and H groups were significantly lower than in the C group. Thus, treatment with cyclophosphamide or ASC can change miRNAs and decrease miR-96-5p and miR-182-5p expression, as well as decreasing the CD138 proportion and the Th1/Th2 ratio, which might be involved in the therapeutic mechanism.