Targeting HMGB1 by ethyl pyruvate ameliorates systemic lupus erythematosus and reverses the senescent phenotype of bone marrow-mesenchymal stem cells.

Targeting HMGB1 by ethyl pyruvate ameliorates systemic lupus erythematosus and reverses the senescent phenotype of bone marrow-mesenchymal stem cells. Aging (Albany NY). 2019 Jul 14;11: Authors: Ji J, Fu T, Dong C, Zhu W, Yang J, Kong X, Zhang Z, Bao Y, Zhao R, Ge X, Sha X, Lu Z, Li J, Gu Z Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs and systems. Mesenchymal stem cells (MSCs) from SLE patients have demonstrated defects such as impaired growth, senescence phenotype and immunomodulatory functions. Some studies have suggested the close connection between inflammation microenvironment and cellular senescence. In the current study, we detected cytokines levels in bone marrow supernatant by the quantitative proteomics analysis, and found the expression of HMGB1 was remarkably increased in bone marrow from SLE patients. Senescence associated-β-galactosidase (SA-β-gal) staining, F-actin staining and flow cytometry were used to detect the senescence of cells. After stimulation of HMGB1 in normal MSCs, the ratio of SA-β-gal positive in BM-MSCs was increased, the organization of cytoskeleton was disordered, and TLR4-NF-κB signaling was activated. Finally, Ethyl pyruvate (EP) (40 mg/kg and 100 mg/kg, three times a week), a high security HMGB1 inhibitor, was injected intraperitoneally to treat MRL/lpr mice for 8 weeks. We demonstrated that EP alleviated the clinical aspects of lupus ne...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research