GRP78/Bip在类风湿性关节炎中的研究进展

Advances in GRP78/Bip in rheumatoid arthritis

GRP78/Bip参与体内绝大多数应激反应,可从细胞内转至细胞外。细胞内GRP78/Bip具有抗凋亡和促细胞增殖作用,细胞外GRP78/Bip具有强大的免疫调节、抗炎和抑制破骨细胞分化和吸收的作用。RA的发生和发展必须克服几个瓶颈,其中病变细胞容易增殖并能同时避免免疫破坏和细胞凋亡是至关重要的一环。因此,针对RA病变细胞内和细胞外GRP78/Bip的研究无疑是理想治疗思路。但目前关于GRP78/Bip在RA中的研究存在较大争议,部分认为可通过抑制体内GRP78/Bip表达,促进病变细胞凋亡,进而达到治疗作用;而另一部分认为可通过增加体内GRP78/Bip,抑制炎症反应,进而达到治疗目的。文章就细胞内外GRP78/Bip在RA中的靶向治疗、抗炎和抗破骨细胞活性及其作用机制假说进行综述。

GRP78/Bip is involved in most of the stress responses in vivo and can be transferred from intracellular to extracellular.Intracellular GRP78/Bip has anti-apoptosis and promote cell proliferation,while extracellular GRP78/Bip has strong immunomodulatory,anti-inflammatory and inhibitory effects on osteoclast differentiation and absorption.The occurrence and development of RA must overcome several bottlenecks,among which the lesion cells are easy to proliferate and can avoid immune destruction and apoptosis at the same time is a crucial link.Therefore,the study of intracellular and extracellular GRP78/Bip in RA lesions is undoubtedly an ideal therapeutic idea.However,there is a great controversy on the study of GRP78/Bip in RA.Some people believe that it can promote the apoptosis of pathological cells by inhibiting the expression of GRP78/Bip in vivo,so as to achieve therapeutic effect.The other part thinks that it can inhibit inflammation by increasing GRP78/Bip in vivo,so as to achieve the purpose of treatment.This paper reviews the targeted therapy,anti-inflammatory and anti-osteoclast activities of GRP78/Bip in RA and the hypotheses of its mechanism of action.