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

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。

Systemic 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.