JAK-STAT signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients.
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 centrifugation. 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 signaling 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.
Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong 226001, China.
Juan
J
Ji
Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong 226001, China.
Yeqing
Y
Wu
Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200000, China.
Yan
Y
Meng
Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong 226001, China.
Lijuan
L
Zhang
Department of Stomatology, Affiliated Hospital of Nantong University, Nantong 226001, China.
Guijuan
G
Feng
Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong 226001, China.
Yunfei
Y
Xia
Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong 226001, China.
Wenrong
W
Xue
Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong 226001, China.
Shuyang
S
Zhao
Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong 226001, China.
Zhifeng
Z
Gu
Department of Immunology, Medical College, Nantong University, Nantong 226001, China.
Xiaoyi
X
Shao
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2
IFN-γ; JAK-STAT signaling; mesenchymal stem cells; senescence; systemic lupus erythematosus