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2015 ; 10
(7
): e0132724
Nephropedia Template TP
gab.com Text
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English Wikipedia
Tacrolimus Protects Podocytes from Injury in Lupus Nephritis Partly by
Stabilizing the Cytoskeleton and Inhibiting Podocyte Apoptosis
#MMPMID26161538
Liao R
; Liu Q
; Zheng Z
; Fan J
; Peng W
; Kong Q
; He H
; Yang S
; Chen W
; Tang X
; Yu X
PLoS One
2015[]; 10
(7
): e0132724
PMID26161538
show ga
OBJECTIVE: Several studies have reported that tacrolimus (TAC) significantly
reduced proteinuria in lupus nephritis (LN) patients and mouse models. However,
the mechanism for this effect remains undetermined. This study explored the
mechanism of how TAC protects podocytes from injury to identify new targets for
protecting renal function. METHODS: MRL/lpr mice were given TAC at a dosage of
0.1 mg/kg per day by intragastric administration for 8 weeks. Urine and blood
samples were collected. Kidney sections (2 ?m) were stained with
hematoxylin-eosin (HE), periodic acid-Schiff base (PAS) and Masson's trichrome
stain. Mouse podocyte cells (MPC5) were treated with TAC and/or TGF-?1 for 48 h.
The mRNA levels and protein expression of synaptopodin and Wilms' tumor 1 (WT1)
were determined by real-time PCR, Western blotting and/or immunofluorescence,
respectively. Flow cytometry was used to detect cell apoptosis with annexin V.
Podocyte foot processes were observed under transmission electron microscopy. IgG
and C3 deposition were assessed with immunofluorescence assays and confocal
microscopy. RESULTS: Synaptopodin expression significantly decreased in MRL/lpr
disease control mice, accompanied by increases in 24-h proteinuria, blood urea
nitrogen, and serum creatinine. TAC, however, reduced proteinuria, improved renal
function, attenuated renal pathology, restored synaptopodin expression and
preserved podocyte numbers. In MPC5 cells, TGF-?1 enhanced F-actin damage in
podocytes and TAC stabilized it. TAC also decreased TGF-?1-induced podocyte
apoptosis in vitro and inhibited foot process fusion in MRL/lpr mice. In
addition, our results also showed TAC inhibited glomerular deposition of IgG and
C3. CONCLUSION: This study demonstrated that TAC reduced proteinuria and
preserved renal function in LN through protecting podocytes from injury partly by
stabilizing podocyte actin cytoskeleton and inhibiting podocyte apoptosis.
|*Apoptosis
[MESH]
|Animals
[MESH]
|Cell Line
[MESH]
|Complement C3/metabolism
[MESH]
|Cytoprotection
[MESH]
|Cytoskeleton/drug effects/*pathology
[MESH]
|Drug Evaluation, Preclinical
[MESH]
|Female
[MESH]
|Immunoglobulin G/metabolism
[MESH]
|Immunosuppressive Agents/pharmacology/therapeutic use
[MESH]