title: The coordinated roles of miR-26a and miR-30c in regulating TGFβ1-induced epithelial-to-mesenchymal transition in diabetic nephropathy.
abstract: MicroRNAs (miRNAs) play vital roles in the development of diabetic nephropathy. Here, we compared the protective efficacies of miR-26a and miR-30c in renal tubular epithelial cells (NRK-52E) and determined whether they demonstrated additive effects in the attenuation of renal fibrosis. TGFβ1 suppressed miR-26a and miR-30c expression but up-regulated pro-fibrotic markers in NRK-52E cells, and these changes were also found in the kidney cortex of 40-week-old diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Bioinformatic analyses and luciferase assays further demonstrated that both miR-26a and miR-30c targeted connective tissue growth factor (CTGF); additionally, Snail family zinc finger 1 (Snail1), a potent epithelial-to-mesenchymal transition (EMT) inducer, was targeted by miR-30c. Overexpression of miR-26a and miR-30c coordinately decreased CTGF protein levels and subsequently ameliorated TGFβ1-induced EMT in NRK-52E cells. Co-silencing of miR-26a and miR-30c exhibited the opposite effect. Moreover, miR-26a and miR-30c co-silenced CTGF to decrease ERK1/2 and p38 MAPK activation. Furthermore, miR-26a was up-regulated in urinary extracellular vesicles of diabetic nephropathy patients. Our study provides evidence for the cooperative roles of miR-26a and miR-30c in the pathogenesis of diabetic nephropathy, and the co-targeting of miR-26a and miR-30c could provide a new direction for diabetic nephropathy treatment.
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Zongji
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Meiping
authors.initials: M
authors.lastname: Guan
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Pang
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Fuping
authors.initials: F
authors.lastname: Lv
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Zhizhou
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000818:Animals; D001483:Base Sequence; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D000067128:Extracellular Vesicles / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D051381:Rats; D020334:Rats, Inbred OLETF; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D055513:Connective Tissue Growth Factor; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors; D053773:Transforming Growth Factor beta1; C556274:MIRN26 microRNA, rat; C528163:MIRN26 microRNA, human; C556157:MIRN30 microRNA, rat; C546086:MIRN30b microRNA, human