Publication: The novel involvement of podocyte autophagic activity in the pathogenesis of lupus nephritis
Authors
Jin, Juan ; Ye, Meiyu ; Zhao, Li ; Zou, Wenli ; Shen, Wei ; Zhang, Hongjuan ; Gong, Jianguang ; He, Qiang
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Publisher
Universidad de Murcia. Departamento de Biología Celular e Histología
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Description
Abstract
Background. Lupus nephritis (LN) is one of
the most common and severe complications in Systemic
lupus erythematosus patients, and the mechanism
underlining the pathogenesis of LN is still unknown.
Autophagy plays vital roles in maintaining cell
homeostasis and is involved in the pathogenesis of many
diseases. In this study, we investigated the role of
autophagy in the progression of LN. Methods.
Autophagic activities in podocytes of both LN patients
(Class IV and V) and mice were evaluated. Podocytes
were observed by electron microscopy, and autophagic
activity was evaluated by immunofluorescence staining
and western blot analysis. Apoptotic activity was
evaluated by immunohistochemistry, TUNEL assays and
flow cytometric analysis. Results. Significantly greater
podocyte injury and discrepant autophagic levels were
observed in LN patients. Differentiated mouse podocytes
in the LN group showed reduced nephrin expression and
increased apoptosis, as well as significantly higher levels
of apoptosis-related proteins (cleaved caspase-3 and
Bax). In the mice LN group, the increased number of
autophagosomes was accompanied by increased LC3-
II/LC3-I ratios and decreased p62, suggesting increased
autophagic and apoptotic activity in podocytes.
Blockade of autophagic activity by 3-MA or siRNAmediated silencing of Atg5 resulted in decreases in LC3-
II/LC3-I ratios, podocyte apoptosis and damage in the
mice LN group. Futhermore, Rapamycin treatment
increased LC3-II/LC3-I ratios, and enhanced LNinduced apoptosis in podocyte from modal animal.
Conclusions. This study demonstrates that autophagic
activity of podocytes is a crucial factor in renal injury by
directly affecting the function of podocyte; thus,
inhibiting this activity during the early stages of LN is
implicated as a potential therapeutic strategy for
delaying the progression of LN. Also, clinical
application in LN needs to consider patients’
pathological type and drugs’ comprehensive
effectiveness.
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