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Comparison of Glomerular Transcriptome Profiles of Adult-Onset Steroid Sensitive
Focal Segmental Glomerulosclerosis and Minimal Change Disease
#MMPMID26536600
Tong J
; Xie J
; Ren H
; Liu J
; Zhang W
; Wei C
; Xu J
; Zhang W
; Li X
; Wang W
; Lv D
; He JC
; Chen N
PLoS One
2015[]; 10
(11
): e0140453
PMID26536600
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OBJECTIVE: To search for biomarkers to differentiate primary focal segmental
glomerulosclerosis (FSGS) and minimal change disease (MCD). METHODS: We isolated
glomeruli from kidney biopsies of 6 patients with adult-onset steroid
sensitiveFSGS and 5 patients with MCD, and compared the profiles of glomerular
transcriptomes between the two groups of patients using microarray analysis.
RESULTS: Analysis of differential expressed genes (DEGs) revealed that
up-regulated DEGs in FSGS patients compared with MCD patients were primarily
involved in spermatogenesis, gamete generation, regulation of muscle contraction,
response to unfolded protein, cell proliferation and skeletal system development.
The down-regulated DEGs were primarily related to metabolic process,
intracellular transport, oxidation/reduction andestablishment of intracellular
localization. We validated the expression of the top 6 up-regulated and top 6
down-regulated DEGs using real-time PCR. Membrane metallo-endopeptidase (MME) is
a down-regulated gene that was previously identified as a key gene for kidney
development. Immunostaining confirmed that the protein expression of MME
decreased significantly in FSGS kidneys compared with MCD kidneys. CONCLUSIONS:
This report was the first study to examine transcriptomes in Chinese patients
with various glomerular diseases. Expressions of MME both in RNA and protein
level decreased significantly in glomeruli of FSGS kidneys compared with MCD
kidneys. Our data suggested that MME might play a role in the normal
physiological function of podocytes and a decrease in MME expression might be
related to podocyte injury. We also identified genes and pathways specific for
FSGS versus MCD, and our data could help identify potential new biomarkers for
the differential diagnosis between these two diseases.
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