Astrocyte elevated gene-1 induces autophagy in diabetic cardiomyopathy through upregulation of KLF4.
KLF4
astrocyte elevated gene-1 (AEG-1)
diabetic cardiomyopathy (DCM)
Journal
Journal of cellular biochemistry
ISSN: 1097-4644
Titre abrégé: J Cell Biochem
Pays: United States
ID NLM: 8205768
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
26
09
2018
accepted:
22
10
2018
pubmed:
7
12
2018
medline:
16
7
2020
entrez:
7
12
2018
Statut:
ppublish
Résumé
Astrocyte elevated gene-1 (AEG-1), also known as metadherin, 3D3, and lysine-rich carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) coisolated, has emerged as an important oncogene that is overexpressed in a variety of cancers. Previous studies revealed that AEG-1 is also involved in multiple physiological and pathological processes, such as development, inflammation, neurodegeneration, migraine, and Huntington's disease. However, the function of AEG-1 in diabetic cardiomyopathy (DCM) has not been reported yet. Therefore, we conducted this study to characterize the potential role and mechanism of AEG-1 in DCM rats. DCM was induced by injections of streptozocin (STZ) in Wistar rats. Rats were randomized to be injected with lentivirus carrying AEG-1 small interfering RNA. Haemodynamic changes of Wistar rats, assessment of cardiac weight index, and the expression of AEG-1 and KLF4 were detected and compared among these three groups. The expressions of AEG-1 and KLF4 in the STZ group were significantly elevated in cardiac tissues compared with the control group. Knockdown of AEG-1 significantly increased the values of left ventricular ejection fraction, ±dp/dt Knockdown of AEG-1 suppresses autophagy in DCM by downregulating the expression of KLF4. This study provide first-notion evidence for the potential value of AEG-1 as a therapeutic target for the treatment of the patients with DCM.
Sections du résumé
BACKGROUND
Astrocyte elevated gene-1 (AEG-1), also known as metadherin, 3D3, and lysine-rich carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) coisolated, has emerged as an important oncogene that is overexpressed in a variety of cancers. Previous studies revealed that AEG-1 is also involved in multiple physiological and pathological processes, such as development, inflammation, neurodegeneration, migraine, and Huntington's disease. However, the function of AEG-1 in diabetic cardiomyopathy (DCM) has not been reported yet. Therefore, we conducted this study to characterize the potential role and mechanism of AEG-1 in DCM rats.
METHODS
DCM was induced by injections of streptozocin (STZ) in Wistar rats. Rats were randomized to be injected with lentivirus carrying AEG-1 small interfering RNA. Haemodynamic changes of Wistar rats, assessment of cardiac weight index, and the expression of AEG-1 and KLF4 were detected and compared among these three groups.
RESULTS
The expressions of AEG-1 and KLF4 in the STZ group were significantly elevated in cardiac tissues compared with the control group. Knockdown of AEG-1 significantly increased the values of left ventricular ejection fraction, ±dp/dt
CONCLUSIONS
Knockdown of AEG-1 suppresses autophagy in DCM by downregulating the expression of KLF4. This study provide first-notion evidence for the potential value of AEG-1 as a therapeutic target for the treatment of the patients with DCM.
Substances chimiques
Crisp3 protein, rat
0
Klf4 protein, rat
0
Kruppel-Like Factor 4
0
Kruppel-Like Transcription Factors
0
Membrane Glycoproteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9709-9715Informations de copyright
© 2018 Wiley Periodicals, Inc.