JAK-STAT signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients

• Published in: Acta biochimica et biophysica Sinica Vol. 49; no. 3; pp. 208 - 215
• Main Authors: Ji, Juan, Wu, Yeqing, Meng, Yan, Zhang, Lijuan, Feng, Guijuan, Xia, Yunfei, Xue, Wenrong, Zhao, Shuyang, Gu, Zhifeng, Shao, Xiaoyi
• Format: Journal Article
• Language: English
• Published: China 01.03.2017
• Subjects: Adolescent; Adult; Bone Marrow - metabolism; Bone Marrow - pathology; Case-Control Studies; Cell Proliferation; Cells, Cultured; Cellular Senescence; Female; Humans; JAK-STAT; Janus Kinase 2 - metabolism; Lupus Erythematosus, Systemic - metabolism; Lupus Erythematosus, Systemic - pathology; Male; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - pathology; Phosphorylation; Signal Transduction; STAT3 Transcription Factor - metabolism; Young Adult; β-半乳糖苷酶; 介导; 信号通路; 患者; 系统性红斑狼疮; 细胞衰老; 骨髓间充质干细胞; senescence; JAK-STAT signaling; IFN-γ; systemic lupus erythematosus; mesenchymal stem cells
• ISSN: 1672-9145; 1745-7270; 1745-7270
• DOI: 10.1093/abbs/gmw134

Previous studies have revealed that bone marrow-mesenchymal stem cells （BM-MSCs） from systemic lupus erythematosus （SLE） patients exhibited early signs of senescence, which may participate in the development of SLE. However, the molecular mechanisms about this phenomenon have not been fully elucidated. In the current study, we aimed to investigate whether Janus kinase （JAK）-signaling transducers and activators of transcription （STAT） signaling mediated the senescence of BM-MSCs from SLE patients. Twelve female SLE patients and healthy subjects were enrolled in the study. All BM-MSCs were isolated by density gradient centdfugation. Western blot analysis was used to test the expression of JAK-STAT signaling molecules. We observed the activity of β-gal of cells, the changes of cytoskeletal structure by F-actin staining, and the distribution of cell cycle by flow cytometry. BM-MSCs from SLE patients showed prominent features of senescence, and abnormal activation of JAK-STAT sig- naling transduction, high level of phosphorylated JAK2, and STAT3. After stimulation of IFN-γ, in normal MSCs, JAK-STAT signaling was activated. The cell volume and the number of senescence-associated β-galactosidase （SA-β-gal） positive in SLE BM-MSCs were increased. The organization of cytoskeleton was nearly disordered. The rate of cell proliferation was decreased. AG490, the inhibitor of JAK2, and knockdown of STAT3 in BM-MSCs, could significantly reverse the senescence. In summary, our study indicated that JAK-STAT signaling pathway may play a critical role in the senescence of SLE BM-MSCs.