Details

Autor(en) / Beteiligte

• Chen, Haifeng
• Shi, Bingyu
• Feng, Xuebing
• Kong, Wei
• Chen, Weiwei
• Geng, Linyu
• Chen, Jinyun
• Liu, Rui
• Li, Xia
• Chen, WanJun
• Gao, Xiang
• Sun, Lingyun

Titel

Leptin and Neutrophil‐Activating Peptide 2 Promote Mesenchymal Stem Cell Senescence Through Activation of the Phosphatidylinositol 3‐Kinase/Akt Pathway in Patients With Systemic Lupus Erythematosus

Ist Teil von

• Arthritis & rheumatology (Hoboken, N.J.), 2015-09, Vol.67 (9), p.2383-2393

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2015

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Objective Mesenchymal stem cells (MSCs) derived from patients with systemic lupus erythematosus (SLE) exhibit enhanced senescence. Cellular senescence has been reported to be induced by several inflammatory cytokines, including interferon‐α (IFNα) and IFNγ, that are involved in the pathogenesis of SLE. We undertook this study to investigate whether the inflammatory environment in SLE could affect MSC senescence. Methods Cellular senescence was measured by staining of senescence‐associated β‐galactosidase and by expression of the cell cycle inhibitors p53 and p21. Eighty cytokines and chemokines in serum from healthy controls and patients with SLE were identified by cytokine antibody array. Results SLE serum promoted senescence of MSCs, which was reversed by the phosphatidylinositol 3‐kinase (PI3K)/Akt signaling inhibitor LY294002 but not by the JAK/STAT inhibitor AG490 and not by the MEK/ERK inhibitor PD98059. Cytokine antibody array analysis revealed that leptin and neutrophil‐activating peptide 2 (NAP‐2) were the 2 factors most significantly elevated in SLE serum compared with normal serum. Blockade of leptin or NAP‐2 in MSC cultures abolished SLE serum–induced senescence, while direct addition of these 2 factors could promote senescence in cultures of normal MSCs. Inhibition of PI3K/Akt signaling with LY294002 reduced leptin‐ and NAP‐2–induced senescence in MSCs. Conclusion Taken together, our data show that leptin and NAP‐2 act synergistically to promote MSC senescence through enhancement of the PI3K/Akt signaling pathway in SLE patients.