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Comparison of Glomerular Transcriptome Profiles of Adult-Onset Steroid Sensitive Focal Segmental Glomerulosclerosis and Minimal Change Disease.

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)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

3D snapshot of PCA analysis of sample distribution based on the transcriptomes.The FSGS group was separated from the MCD group. Moreover, FSGS patients were far from MCD patients, which indicated dramatic transcriptomic changes in FSGS patients compared with MCD patients. F1 ~ F6 (green sphere) indicated FSGS patients; M1 ~ M5 (red sphere) indicated MCD patients.
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pone.0140453.g004: 3D snapshot of PCA analysis of sample distribution based on the transcriptomes.The FSGS group was separated from the MCD group. Moreover, FSGS patients were far from MCD patients, which indicated dramatic transcriptomic changes in FSGS patients compared with MCD patients. F1 ~ F6 (green sphere) indicated FSGS patients; M1 ~ M5 (red sphere) indicated MCD patients.

Mentions: We performed microarray analysis of glomerular gene expression from FSGS and MCD patients and identified DEGs between these two groups. We performed PCA analyses to identify sample correlations using the raw data obtained from microarray studies (Fig 4). Comparisons of the gene expression profiles between FSGS and MCD patients revealed several patterns of disease-specific changes between the two diseases (Fig 5). Gene ontology and pathway analyses were also performed in the DEGs.


Comparison of Glomerular Transcriptome Profiles of Adult-Onset Steroid Sensitive Focal Segmental Glomerulosclerosis and Minimal Change Disease.

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)

3D snapshot of PCA analysis of sample distribution based on the transcriptomes.The FSGS group was separated from the MCD group. Moreover, FSGS patients were far from MCD patients, which indicated dramatic transcriptomic changes in FSGS patients compared with MCD patients. F1 ~ F6 (green sphere) indicated FSGS patients; M1 ~ M5 (red sphere) indicated MCD patients.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4633097&req=5

pone.0140453.g004: 3D snapshot of PCA analysis of sample distribution based on the transcriptomes.The FSGS group was separated from the MCD group. Moreover, FSGS patients were far from MCD patients, which indicated dramatic transcriptomic changes in FSGS patients compared with MCD patients. F1 ~ F6 (green sphere) indicated FSGS patients; M1 ~ M5 (red sphere) indicated MCD patients.
Mentions: We performed microarray analysis of glomerular gene expression from FSGS and MCD patients and identified DEGs between these two groups. We performed PCA analyses to identify sample correlations using the raw data obtained from microarray studies (Fig 4). Comparisons of the gene expression profiles between FSGS and MCD patients revealed several patterns of disease-specific changes between the two diseases (Fig 5). Gene ontology and pathway analyses were also performed in the DEGs.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus