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Increased autophagy is cytoprotective against podocyte injury induced by antibody and interferon-? in lupus nephritis.


ABSTRACT: OBJECTIVE:More recent studies suggested that defects in autophagy contribute to the pathogenesis of SLE, especially in adaptive immunity. Occurrence and progression of lupus nephritis (LN) is the end result of complex interactions between regulation of immune responses and pathological process by renal resident cells, but there is still a lot of missing information for an establishment on the role of autophagy in pathogenesis of LN and as a therapy target. METHODS:Systemic and organ-specific aetiologies of autophagy were first evaluated by autophagy protein quantification in tissue homogenates in MRL lpr/lpr lupus prone and female C57BL mice. Analysis of gene expression was also adopted in human blood and urine sediments. Then, some key mediators of the disease, including complement inactivated serum, IgG from patients with LN (IgG-LN) and interferon (IFN)-? were chosen to induce podocyte autophagy. Podocyte injuries including apoptosis, podocin derangement, albumin filtration and wound healing were monitored simultaneously with autophagy steady-state and flux. RESULTS:Elevated LC3B in kidney homogenates and increased autophagosomes in podocyte from MRL lpr/lpr were observed. In humans, mRNA levels of some key autophagy genes were increased in blood and urinary sediments, and podocyte autophagosomes were observed in renal biopsies from patients with LN. Complement inactivated serum, IgG-LN and IFN-? could induce podocyte autophagy in a time-dependent and dosage-dependent manner, and by reactive oxygen species production and mTORC1 inhibition, respectively. Autophagy inhibition aggravated podocyte damage whereas its inducer relieved the injury. CONCLUSION:Podocyte autophagy is activated in lupus-prone mice and patients with lupus nephritis. Increased autophagy is cytoprotective against antibody and interferon-? induced podocyte injury.

SUBMITTER: Qi YY 

PROVIDER: S-EPMC6800572 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Increased autophagy is cytoprotective against podocyte injury induced by antibody and interferon-α in lupus nephritis.

Qi Yuan-Yuan YY   Zhou Xu-Jie XJ   Cheng Fa-Juan FJ   Hou Ping P   Ren Ya-Li YL   Wang Su-Xia SX   Zhao Ming-Hui MH   Yang Li L   Martinez Jennifer J   Zhang Hong H  

Annals of the rheumatic diseases 20180912 12


<h4>Objective</h4>More recent studies suggested that defects in autophagy contribute to the pathogenesis of SLE, especially in adaptive immunity. Occurrence and progression of lupus nephritis (LN) is the end result of complex interactions between regulation of immune responses and pathological process by renal resident cells, but there is still a lot of missing information for an establishment on the role of autophagy in pathogenesis of LN and as a therapy target.<h4>Methods</h4>Systemic and org  ...[more]

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