自噬
狼疮性肾炎
足细胞
系统性红斑狼疮
细胞生物学
免疫学
炎症体
炎症
生物
医学
癌症研究
肾
细胞凋亡
疾病
内科学
内分泌学
生物化学
蛋白尿
作者
Manuel Alfredo Podestà,Irene Faravelli,Claudio Ponticelli
标识
DOI:10.1016/j.autrev.2022.103132
摘要
Autophagy is a highly regulated process wherein an unwanted cargo of damaged and dysfunctional cytoplasmic components is removed, delivered to lysosomes for degradation, and released back into the cytoplasm. Accumulating evidence suggests an important role of autophagy in the pathophysiology of systemic lupus erythematosus, with profound effects on both innate and adaptive immunity. Autophagy downregulation results in the inhibition of antigen presenting cells, reduced release of neutrophil extracellular traps and decreased activation of effector T and B cells, leading to reduced autoantibody production and attenuated type 1 interferon signaling. However, defective autophagy may accelerate the production of other inflammatory cytokines and reduce the clearance of apoptotic cells, promoting lupus development. In addition, autophagy dysfunction can concur to the pathogenesis of kidney injury in lupus nephritis. Autophagy is a pivotal mechanism to maintain podocyte integrity and endothelial cell survival. Several animal models have demonstrated that defective autophagy leads to podocyte injury and can promote an endothelial pro-inflammatory and atherogenic phenotype. Moreover, autophagy is a key homeostatic regulator of renal tubular cells, and recent evidence has pointed out that chronic autophagy deficiency may accelerate kidney fibrosis. Targeting autophagy may theoretically improve lupus nephritis outcomes, but novel, non-invasive methods to measure and monitor autophagic activity are urgently needed. In addition, the extent and timing of autophagy inhibition still require additional studies before clinical translation may be attempted. In this review, we will also discuss the effect of several clinically available drugs that can regulate the autophagic flux and their effect in lupus nephritis patients.
科研通智能强力驱动
Strongly Powered by AbleSci AI