Publication: STIM promotes the epithelial-mesenchymal transition of podocytes through regulation of FcγRII activity in diabetic nephropathy
Authors
Jin, Juan ; Ye, Meiyu ; Hu, Kang ; Gong, Jianguang ; He, Qiang
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Publisher
Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
DOI: 10.14670/HH-18-068
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info:eu-repo/semantics/article
Description
Abstract
Background. Diabetic nephropathy (DN) is a
serious complication in diabetic patients and has been
considered as the main cause of end-stage renal disease.
However, there are no studies on the role of stromal
interaction molecule (STIM) and its two subtypes,
STIM1 and STIM2, in the epithelial-to-mesenchymal
transition (EMT) of podocytes induced by diabetic
kidney disease (DKD). The present study suggests for
the first time that STIM inhibition decreases DKDinduced EMT.
Methods. All DKD patients were diagnosed based
on renal biopsies carried out at the Department of
Nephrology, Zhejiang Provincial People’s Hospital and
selected using the Mayo Clinic/Renal Pathology Society
Consensus Report on Pathologic Classification,
Diagnosis, and Reporting of GN. Images were taken and
the number of positive puncta in cells was analyzed
using software equipped for immunofluorescence
microscopy. STIM1, STIM2, FcγRIIa, FcγRIIb,
Nephrin, CTGF, and α-SMA protein levels were
detected by Western blotting analysis using the
corresponding antibodies. The viability of cells was
measured using CCK-8 assays. Absorbance at 450 nm
was measured with a Multiskan FC Microplate Reader
(Thermo Scientific, USA) and the results were
normalized to those of untreated cells. All statistical
analyses were performed using SPSS 19.0 software
(Stanford University, Stanford, CA, USA).
Results. A total of 30 DKD patients and 30 control
patients were enrolled in the study. We found that the
level of urine protein in patients and db/db diabetic mice
is higher than control group and the levels of STIM1 and
2 significantly increased in DKD groups. We also
demonstrated that STIM is upregulated during DKD
injury. Next, we discovered that DKD-induced podocyte
EMT is related to STIM overexpression in vivo and in
vitro. Further research demonstrated that STIM siRNA
reverses podocytes from DKD-induced injury and EMT
and reverses FcγRII activity in HG-treated podocytes.
Conclusion. Our study suggests that STIM and
FcγRII play an essential role in the regulation of DKDinduced podocyte EMT. STIM is an essential component
of FcγR activation and inhibition of STIM-mediated
signaling pathway might be a new strategy to treat IgGdependent renal diseases.
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Citation
Histology and Histopathology, Vol.34, nº6, (2019)
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/