Open AccessRNA‐seq profiling of tubulointerstitial tissue reveals a potential therapeutic role of dual anti‐phosphatase 1 in glomerulonephritis
Author(s) -
Park Sehoon,
Lee Hajeong,
Lee Jeongha,
Lee Sangmoon,
Cho Semin,
Huh Hyeok,
Kim Joo Young,
Park Minkyoung,
Lee Soojin,
Kim Yaerim,
Choi Murim,
Joo Kwon Wook,
Kim Yon Su,
Yang Seung Hee,
Kim Dong Ki
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17340
Subject(s) - glomerulonephritis , dual specificity phosphatase , phosphatase , profiling (computer programming) , rna seq , rna , computational biology , biology , pathology , cancer research , medicine , kidney , biochemistry , enzyme , genetics , gene , transcriptome , computer science , gene expression , operating system
Transcriptome profiling of tubulointerstitial tissue in glomerulonephritis may reveal a potential tubulointerstitial injury‐related biomarker. We profiled manually microdissected tubulointerstitial tissue from biopsy cores of 65 glomerulonephritis cases, including 43 patients with IgA nephropathy, 3 with diabetes mellitus nephropathy, 3 with focal segmental glomerulosclerosis, 3 with lupus nephritis, 4 with membranous nephropathy and 9 with minimal change disease, and additional 22 nephrectomy controls by RNA sequencing. A potential biomarker was selected based on the false discovery rate, and experiments were performed in TNF‐α‐stimulated primary cultured human tubular epithelial cells (hTECs). We identified 3037 genes with low expression and 2852 genes with high expression in the disease samples compared to the controls. Dual‐specificity phosphatase 1 (DUSP1) exhibited universal low expression in various diseases (log2 fold change, −3.87), with the lowest false discovery rate (7.03E‐132). In further experimental validation study, DUSP1 overexpression ameliorated inflammatory markers related to MAP kinase pathways in hTECs, while pharmacologic inhibition of DUSP1 increased these markers. The combination of DUSP1 overexpression with low‐concentration corticosteroid treatment resulted in more potent suppression of inflammation than high‐concentration corticosteroid treatment alone. The profiled transcriptomes provide insights into the pathophysiology of tubulointerstitial injury in kidney diseases and may reveal a potential therapeutic biomarker.