Comparison of glomerular transcriptome profiles of adult-onset steroid sensitive focal segmental glomerulosclerosis and minimal change disease

Jun Tong, Jingyuan Xie, Hong Ren, Jian Liu, Weijia Zhang, Chengguo Wei, Jing Xu, Wen Zhang, Xiao Li, Weiming Wang, Danfeng Lv, John Cijiang He, Nan Chen

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 sensitive FSGS 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.

Original languageEnglish
Article numbere0140453
JournalPLoS ONE
Volume10
Issue number11
DOIs
StatePublished - 4 Nov 2015

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