miR-503/Apelin-12 mediates high glucose-induced microvascular endothelial cells injury via JNK and p38MAPK signaling pathway.

Apelin-12 Diabetic angiopathy Diabetic angiopathy, DA Enzyme linked immunosorbent assay, ELISA High glucose, HG JNK MicroRNAs, miRNAs Quantitative Real-time-PCR, qPCR malondialdehyde, MDA miR-503 mutant, Mut p38MAPK reactive oxygen species, ROS superoxide dismutase, SOD wild type, WT

Journal

Regenerative therapy
ISSN: 2352-3204
Titre abrégé: Regen Ther
Pays: Netherlands
ID NLM: 101709085

Informations de publication

Date de publication:
Jun 2020
Historique:
received: 13 08 2019
revised: 30 10 2019
accepted: 03 12 2019
entrez: 29 1 2020
pubmed: 29 1 2020
medline: 29 1 2020
Statut: epublish

Résumé

Diabetic patients are often accompanied by complications of diabetic vascular disease, which could lead to heart failure or stroke. In this work, we explored the role of miR-503/Apelin-12 in diabetic angiopathy (DA) ELISA and qPCR were applied to assess the expression of miR-503 and Apelin-12 in high glucose (HG)-treated microvascular endothelial cells (HMEC-1). The effects of miR-503 on apoptosis, inflammation and oxidative stress were assessed by flow cytometry, western blotting, qPCR, and ELISA. The interaction between miR-503 and Apelin-12 was evaluated by dual-luciferase reporter assay, qPCR and ELISA, respectively. Western blotting was performed to examine the function of miR-503/Apelin-12 on JNK and p38MAPK activation. MiR-503 was markedly increased and Apelin-12 was decreased in HG-treated HMEC-1 cells. MiR-503 inhibitor significantly assuaged apoptosis, inflammation and oxidative stress in HMEC-1 cells. MiR-503 could specifically bind to the 3'UTR of Apelin and inversely downregulate Apelin-12 expression. Furthermore, Apelin-12 suppressed apoptosis, inflammation and oxidative stress. Inhibition of Apelin-12 could partially reverse the decrease of p-JNK and p-p38 expression levels induced by miR-503 suppression. In HG-induced microvascular cells injury, miR-503/Apelin-12 enhances inflammation and oxidative stress by regulating JNK and p38MAPK pathway, suggesting a potential therapeutic target for DA.

Identifiants

pubmed: 31989001
doi: 10.1016/j.reth.2019.12.002
pii: S2352-3204(19)30159-2
pmc: PMC6970136
doi:

Types de publication

Journal Article

Langues

eng

Pagination

111-118

Informations de copyright

© 2020 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.

Déclaration de conflit d'intérêts

Authors have declared no conflict of interests.

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Auteurs

Kai Chen (K)

Department of Endocrinology 2, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 41005, PR China.

Xin-Lan Zhao (XL)

Department of Endocrinology 2, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 41005, PR China.

Lang-Bo Li (LB)

Department of Endocrinology 2, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 41005, PR China.

Ling-Yun Huang (LY)

Department of Endocrinology 2, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 41005, PR China.

Zhuo Tang (Z)

Department of Endocrinology 2, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 41005, PR China.

Juan Luo (J)

Department of Endocrinology 2, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 41005, PR China.

Li Yang (L)

Department of Endocrinology 2, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 41005, PR China.

Ai-Ping Qin (AP)

Department of Endocrinology 2, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 41005, PR China.

Fang Hu (F)

Department of Respiratory 4, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 41005, PR China.

Classifications MeSH