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Tytuł:
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Circ_WBSCR17 aggravates inflammatory responses and fibrosis by targeting miR-185-5p/SOX6 regulatory axis in high glucose-induced human kidney tubular cells.
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Autorzy:
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Li G; Department of Basic Medica, Jiangsu College of Nursing, Huaian, Jiangsu 223005, China.
Qin Y; Department of Basic Medica, Jiangsu College of Nursing, Huaian, Jiangsu 223005, China.
Qin S; Department of Basic Medica, Jiangsu College of Nursing, Huaian, Jiangsu 223005, China.
Zhou X; Department of Basic Medica, Jiangsu College of Nursing, Huaian, Jiangsu 223005, China.
Zhao W; Department of Basic Medica, Jiangsu College of Nursing, Huaian, Jiangsu 223005, China.
Zhang D; College of Pharmacy and Traditional Chinese Medicine, Jiangsu College of Nursing, Huaian, Jiangsu 223005, China. Electronic address: .
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Źródło:
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Life sciences [Life Sci] 2020 Oct 15; Vol. 259, pp. 118269. Date of Electronic Publication: 2020 Aug 13.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
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MeSH Terms:
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Diabetic Nephropathies/*metabolism
Kidney Tubules/*metabolism
MicroRNAs/*metabolism
N-Acetylgalactosaminyltransferases/*genetics
RNA, Circular/*metabolism
SOXD Transcription Factors/*metabolism
Animals ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Diabetes Mellitus, Experimental/genetics ; Diabetes Mellitus, Experimental/metabolism ; Diabetic Nephropathies/genetics ; Diabetic Nephropathies/pathology ; Disease Models, Animal ; Epithelial Cells/metabolism ; Fibrosis/genetics ; Fibrosis/metabolism ; Glucose/metabolism ; Humans ; Inflammation/genetics ; Inflammation/metabolism ; Inflammation/pathology ; Kidney Tubules/pathology ; Kidney Tubules/physiology ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs/genetics ; N-Acetylgalactosaminyltransferases/metabolism ; RNA, Circular/genetics ; SOXD Transcription Factors/genetics ; Polypeptide N-acetylgalactosaminyltransferase
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Contributed Indexing:
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Keywords: Diabetic nephropathy; HK-2; High glucose; SOX6; circ_WBSCR17; miR-185-5p
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Substance Nomenclature:
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0 (MIRN185 microRNA, human)
0 (MicroRNAs)
0 (RNA, Circular)
0 (SOX6 protein, human)
0 (SOXD Transcription Factors)
EC 2.4.1.- (N-Acetylgalactosaminyltransferases)
IY9XDZ35W2 (Glucose)
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Entry Date(s):
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Date Created: 20200818 Date Completed: 20201104 Latest Revision: 20231213
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Update Code:
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20240105
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DOI:
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10.1016/j.lfs.2020.118269
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PMID:
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32798559
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Background: Diabetic nephropathy (DN), a severe microvascular complication of diabetes, has complex pathogenesis. Circular RNAs (circRNAs) exert broad biological functions on human diseases. This study intended to explore the role and mechanism of circ_WBSCR17 in DN.
Methods: DN mice models were constructed using streptozotocin injection, and DN cell models were assembled using high glucose (HG) treatment in human kidney 2 cells (HK-2). The expression of circ_WBSCR17, miR-185-5p and SRY-Box Transcription Factor 6 (SOX6) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of SOX6 and fibrosis markers were examined by western blot. The release of inflammatory cytokines, cell proliferation and apoptosis, were assessed by enzyme-linked immunosorbent assay (ELISA), cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The predicted interaction between miR-185-5p and circ_WBSCR17 or SOX6 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.
Result: Circ_WBSCR17 was highly expressed in DN mice models and HG-induced HK-2 cells. Circ_WBSCR17 knockdown or SOX6 knockdown promoted cell proliferation and blocked cell apoptosis, inflammatory responses and fibrosis, while circ_WBSCR17 overexpression or SOX6 overexpression conveyed the opposite effects. MiR-185-5p was a target of circ_WBSCR17 and directly bound to SOX6. MiR-185-5p could reverse the role of circ_WBSCR17 or SOX6. Moreover, the expression of SOX6 was modulated by circ_WBSCR17 through intermediating miR-185-5p.
Conclusion: Circ_WBSCR17 triggered the dysfunction of HG-induced HK-2 cells, including inflammatory responses and fibrosis, which was accomplished via the miR-185-5p/SOX6 regulatory axis.
Competing Interests: Declaration of competing interest The authors declare that they have no financial conflicts of interest.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
