lncRNA ZEB1-AS1 inhibits high glucose-induced EMT and fibrogenesis by regulating the miR-216a-5p/BMP7 axis in diabetic nephropathy.
Bone Morphogenetic Protein 7
/ metabolism
Cells, Cultured
Diabetic Nephropathies
/ genetics
Down-Regulation
Epithelial-Mesenchymal Transition
/ physiology
Humans
MicroRNAs
/ metabolism
RNA, Long Noncoding
/ physiology
Real-Time Polymerase Chain Reaction
Up-Regulation
Zinc Finger E-box-Binding Homeobox 1
/ metabolism
Journal
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
ISSN: 1414-431X
Titre abrégé: Braz J Med Biol Res
Pays: Brazil
ID NLM: 8112917
Informations de publication
Date de publication:
2020
2020
Historique:
received:
05
10
2019
accepted:
06
01
2020
entrez:
16
4
2020
pubmed:
16
4
2020
medline:
27
5
2020
Statut:
epublish
Résumé
Diabetic nephropathy (DN) is one of the leading causes of mortality in diabetic patients. Long non-coding RNA zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) plays a crucial role in the development of various diseases, including DN. However, the molecular mechanism of ZEB1-AS1 in DN pathogenesis remains elusive. An in vitro DN model was established by treating HK-2 cells with high glucose (HG). Quantitative polymerase chain reaction (qRT-PCR) was utilized to detect the expression levels of ZEB1-AS1, microRNA-216a-5p (miR-216a-5p), and bone morphogenetic protein 7 (BMP7). Western blot assay was used to evaluate the protein levels of BMP7, epithelial-to-mesenchymal transition (EMT)-related proteins, and fibrosis markers. Additionally, the interaction among ZEB1-AS1, miR-216a-5p, and BMP7 was predicted by MiRcode (http://www.mircode.org) and starBase 2.0 (omics_06102, omicX), and confirmed by luciferase reporter assay. ZEB1-AS1 and BMP7 were down-regulated, while miR-216a-5p was highly expressed in kidney tissues of DN patients. Consistently, HG treatment decreased the levels of ZEB1-AS1 and BMP7, whereas HG increased miR-216a-5p expression in HK-2 cells in a time-dependent manner. ZEB1-AS1 upregulation inhibited HG-induced EMT and fibrogenesis. Furthermore, ZEB1-AS1 directly targeted miR-216a-5p, and overexpression of miR-216a-5p restored the inhibitory effects of ZEB1-AS1 overexpression on EMT and fibrogenesis. BMP7 was negatively targeted by miR-216a-5p. In addition, ZEB1-AS1 suppressed HG-induced EMT and fibrogenesis by regulating miR-216a-5p and BMP-7. lncRNA ZEB1-AS1 inhibited high glucose-induced EMT and fibrogenesis via regulating miR-216a-5p/BMP7 axis in diabetic nephropathy, providing a potential target for DN therapy.
Identifiants
pubmed: 32294702
pii: S0100-879X2020000400607
doi: 10.1590/1414-431X20209288
pmc: PMC7162581
pii:
doi:
Substances chimiques
Bone Morphogenetic Protein 7
0
MicroRNAs
0
RNA, Long Noncoding
0
ZEB1 protein, human
0
Zinc Finger E-box-Binding Homeobox 1
0
Types de publication
Journal Article
Retracted Publication
Langues
eng
Sous-ensembles de citation
IM
Pagination
e9288Commentaires et corrections
Type : RetractionIn
Références
J Histochem Cytochem. 2012 Dec;60(12):976-86
pubmed: 23103723
Cytokine Growth Factor Rev. 2011 Jun;22(3):131-9
pubmed: 21757394
Clin Sci (Lond). 2019 Jun 20;133(12):1321-1339
pubmed: 31221822
Pharmacol Res. 2019 Apr;142:22-29
pubmed: 30742900
Int J Mol Sci. 2019 Apr 23;20(8):
pubmed: 31018516
Mol Med Rep. 2017 Sep;16(3):3308-3314
pubmed: 28765970
Front Biosci. 2008 May 01;13:4726-39
pubmed: 18508541
J Biol Chem. 2010 Oct 29;285(44):34004-15
pubmed: 20713358
Cell. 2018 Jan 25;172(3):393-407
pubmed: 29373828
J Diabetes Res. 2017;2017:7242384
pubmed: 28695133
Arch Physiol Biochem. 2019 Jan 19;:1-4
pubmed: 30663414
Horm Metab Res. 2009 Aug;41(8):585-93
pubmed: 19452424
Int J Mol Sci. 2019 Jun 24;20(12):
pubmed: 31238513
RNA Biol. 2018;15(11):1399-1409
pubmed: 30381983
Nephrol Dial Transplant. 2015 Aug;30 Suppl 4:iv35-42
pubmed: 26209736
J Mol Med (Berl). 2004 Mar;82(3):175-81
pubmed: 14752606
Cytokine Growth Factor Rev. 2011 Aug;22(4):221-9
pubmed: 21924665
Clin Sci (Lond). 2015 Feb;128(4):269-80
pubmed: 25200314
Cells. 2015 Oct 09;4(4):631-52
pubmed: 26473930
Evid Based Complement Alternat Med. 2019 Mar 7;2019:3513179
pubmed: 30984273
Dev Dyn. 2018 Mar;247(3):405-431
pubmed: 28691356
Int J Mol Med. 2019 Jul;44(1):196-206
pubmed: 31115480
Curr Med Chem. 2015;22(24):2858-70
pubmed: 26119175
Cell Prolif. 2018 Feb;51(1):
pubmed: 29226522
Nat Rev Mol Cell Biol. 2019 Aug;20(8):474-489
pubmed: 31182864
Am J Transl Res. 2016 Oct 15;8(10):4095-4105
pubmed: 27829995
Int J Mol Sci. 2019 Jun 11;20(11):
pubmed: 31212704
Cell Death Dis. 2019 Feb 12;10(2):129
pubmed: 30755599
Diab Vasc Dis Res. 2014 May 19;11(4):251-261
pubmed: 24845071
J Cell Physiol. 2017 Dec;232(12):3261-3272
pubmed: 28079253
Mol Ther Nucleic Acids. 2018 Sep 7;12:741-750
pubmed: 30121551
Mol Cancer. 2016 Feb 24;15:18
pubmed: 26905733
J Am Soc Nephrol. 2006 Sep;17(9):2504-12
pubmed: 16899516
Curr Opin Nephrol Hypertens. 2004 Jul;13(4):417-22
pubmed: 15199292