ABSTRACT
BACKGROUND: Systemic lupus erythematosus (SLE) is a multisystem disease that is characterized by the appearance of serum autoantibodies. No effective treatment for SLE currently exists. METHODS: We used human umbilical cord mesenchymal stem cell (H-UC-MSC) transplantation to treat B6.Fas mice. RESULTS: After four rounds of cell transplantation, we observed a statistically significant decrease in the levels of mouse anti-nuclear, anti-histone, and anti-double-stranded DNA antibodies in transplanted mice compared with controls. The percentage of CD4(+)CD25(+)Foxp3(+) T cells in mouse peripheral blood significantly increased after H-UC-MSC transplantation. CONCLUSIONS: The results showed that H-UC-MSCs could repair lesions in B6.Fas mice such that all of the relevant disease indicators in B6.Fas mice were restored to the levels observed in normal C57BL/6 mice.
Subject(s)
Lupus Erythematosus, Systemic/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , T-Lymphocytes, Regulatory/immunology , Umbilical Cord/cytology , Animals , Antibodies, Antinuclear/blood , CD4 Antigens/metabolism , DNA/immunology , Forkhead Transcription Factors/metabolism , Histones/immunology , Humans , Interleukin-2 Receptor alpha Subunit/metabolism , Lupus Erythematosus, Systemic/immunology , Lymphocyte Count , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Transplantation, HeterologousABSTRACT
Insulin resistance is a major player in the pathogenesis of type II diabetes, the metabolic syndrome, and obesity. SOCS3 plays an important role in the development of insulin resistance. To investigate the role of SOCS3 in porcine adipocyte insulin signaling, we first detected the effect of insulin on SOCS3 mRNA and protein expression in porcine primary adipocytes by real-time RT-PCR and Western blotting. Then, we constructed a recombinant adenovirus encoding SOCS3 gene (Ad-SOCS3) which was used to infect differentiated porcine primary adipocytes for 3 days. The expression and phosphorylation of main insulin signaling components were detected by Western blotting. The results showed that 100 nM insulin could induce SOCS3 mRNA expression but not protein expression, and overexpression of SOCS3 decreased IRS1 protein level, insulin-stimulated IRS1 tyrosine phosphorylation, PI3K activation, and Akt phosphorylation, but increased IRS1 serine phosphorylation in porcine primary adipocytes. These results indicate that SOCS3 is an important negative regulator of insulin signaling in porcine adipocytes. Thus, SOCS3 may be a novel therapeutic target for the prevention or treatment of insulin resistance and type II diabetes.
