MicroRNA-770-5p is involved in the development of diabetic nephropathy through regulating podocyte apoptosis by targeting TP53 regulated inhibitor of apoptosis 1.
Eur Rev Med Pharmacol Sci
; 23(3): 1248-1256, 2019 Feb.
Article
de En
| MEDLINE
| ID: mdl-30779094
ABSTRACT
OBJECTIVE:
Diabetic nephropathy (DN) is a major diabetic micro-vascular complication, and podocyte apoptosis induced by high glucose (HG) is a typical early feature of DN. Studies have shown that microRNAs (miRNAs) play a crucial role in the pathogenesis of DN. The purpose of the current study was to explore the role and molecular mechanism of miR-770-5p in podocyte apoptosis in DN. PATIENTS AND MATERIALS ANDMETHODS:
In vitro podocyte model of DN was conducted by treatment conditionally immortalized mouse podocytes with HG (30 mM D-glucose). The level of miR-770-5p in podocytes was detected using quantitative real-time PCR (qRT-PCR), and protein levels were measured using Western blot assay in our current study. The relationship between miR-770-5p and TP53 regulated inhibitor of apoptosis 1 (TRIAP1) was revealed by TargetScan and dual luciferase reporter assay. Cell proliferation ability and cell apoptosis were determined by using cell counting kit-8 (CCK-8) assay and flow cytometer (FCM), respectively.RESULTS:
We found that miR-770-5p was significantly upregulated in podocytes under HG condition. TRIAP1 was a target gene of miR-770-5p and it was down-regulated in podocytes by HG treatment. Further analysis indicated that HG induced cell proliferation ability reduction, cell apoptosis enhancement and apoptotic peptidase activating factor 1(APAF1)/Caspase9 pathway exaltation in podocytes were prevented by miR-770-5p down-regulation. More importantly, the results showed that all the effects of miR-770-5p inhibitor on HG induced podocytes were eliminated by TRIAP1 silencing. S.-Z. Zhang, X.-J. Qiu, S.-S. Dong, L.-N. Zhou, Y. Zhu, M.-D. Wang, L.-W. Jin We showed that miR-770-5p was upregulated in the in vitro model of DN, and it might promote the development of DN through regulating podocyte apoptosis by targeting TRIAP1.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Apoptose
/
MicroARN
/
Protéines et peptides de signalisation intracellulaire
/
Néphropathies diabétiques
/
Podocytes
/
Modèles biologiques
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
Eur Rev Med Pharmacol Sci
Sujet du journal:
FARMACOLOGIA
/
TOXICOLOGIA
Année:
2019
Type de document:
Article
Pays d'affiliation:
Chine