系统性红斑狼疮患者骨髓间充质干细胞衰老的研究进展
Senescence of bone marrow mesenchymal stem cells in patients with systemic lupus erythematosus
摘要系统性红斑狼疮(SLE)是一种累及多器官、多系统的临床表现多样的慢性自身免疫性疾病.骨髓间充质干细胞(BMSC)是一类中胚层来源的非造血干细胞,是造血微环境的重要成分.多项研究表明,SLE是一种干细胞疾病,不仅造血干细胞存在异常,间充质细胞(MSC)也存在异常,具体表现为:生物学特征改变、细胞骨架及超微结构异常、端粒缩短、端粒酶及SA-β-Gal活性增强、分化能力减弱、免疫调节功能异常等衰老特征;其衰老机制可能与MSC内p53/p21cip1、p16INK4a/Rb、p27kip1/pTEN表达上调、ROS水平升高、内质网应激、表观遗传学改变等有关.
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abstractsSystemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multi-organ and multisystemic involvement and various clinical manifestations.Bone marrow mesenchymal stem cells (BM-MSCs),a kind of non-hematopoietic stem cells originating from the mesoderm,are key components of hematopoietic microenvironment.Recent studies have indicated that SLE is a disorder of stem cells.Both hematopoietic and mesenchymal stem cells (MSCs) are abnormal in SLE,which mainly manifests as changes of biological characteristics,abnormal cytoskeleton and ultrastructure,shortened telomeres,increased telomerase and SA-β-Gal acitivity,decreased differentiative ability,aberrant immunoregulatory effect,and other features of senescence.The mechanism of MSC aging may be related to up-regulated expressions of aging-related genes p53/p21cip1,p16INK4a/Rb and p27kip1/pTEN,elevated levels of reactive oxygen species (ROS),endoplasmic reticulum stress,epigenetic alterations,etc.
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