自身免疫性风湿性疾病包括一组以非器官特异性炎症为特征的免疫相关病症。这些疾病包括系统性红斑狼疮(SLE),类风湿性关节炎(RA),强直性脊柱炎(AS),痛风,在其他人中。通常涉及血液系统,这些疾病也可能影响多个器官和系统。自身免疫性风湿免疫性疾病的发病机制复杂,不同的病因,都与免疫功能障碍有关。目前这种类型疾病的治疗选择相对有限,并伴有某些副作用。因此,目前的紧迫挑战仍然是确定这些疾病的新治疗靶点。甾醇调节元件结合蛋白(SREBP)是基本的螺旋-环-螺旋-亮氨酸拉链转录因子,可调节脂质和胆固醇生物合成相关基因的表达。SREBPs的表达和转录活性可以通过细胞外刺激如多不饱和脂肪酸来调节,氨基酸,葡萄糖,和能量途径,包括AKT-mTORC和AMP激活的蛋白激酶(AMPK)。研究表明,SREBPs在调节脂质代谢、细胞因子产生,炎症,和生发中心B(GCB)细胞的增殖。这些功能在风湿病和免疫性疾病的发病机理中具有重要意义(图形摘要)。因此,本文综述了SREBPs在SLE发病中的潜在机制,RA,和痛风,基于对其功能的探索。
Autoimmune rheumatic diseases comprise a group of immune-related disorders characterized by non-organ-specific inflammation. These diseases include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), gout, among others. Typically involving the hematologic system, these diseases may also affect multiple organs and systems. The pathogenesis of autoimmune rheumatic immune diseases is complex, with diverse etiologies, all associated with immune dysfunction. The current treatment options for this type of disease are relatively limited and come with certain side effects. Therefore, the urgent challenge remains to identify novel therapeutic targets for these diseases. Sterol regulatory element-binding proteins (SREBPs) are basic helix-loop-helix-leucine zipper transcription factors that regulate the expression of genes involved in lipid and cholesterol biosynthesis. The expression and transcriptional activity of SREBPs can be modulated by extracellular stimuli such as polyunsaturated fatty acids, amino acids, glucose, and energy pathways including AKT-mTORC and AMP-activated protein kinase (AMPK). Studies have shown that SREBPs play roles in regulating lipid metabolism, cytokine production, inflammation, and the proliferation of germinal center B (GCB) cells. These functions are significant in the pathogenesis of rheumatic and immune diseases (Graphical abstract). Therefore, this paper reviews the potential mechanisms of SREBPs in the development of SLE, RA, and gout, based on an exploration of their functions.