KLF9 Aggravates Streptozotocin-Induced Diabetic Cardiomyopathy by Inhibiting PPARγ/NRF2 Signalling Article Swipe
Fangfang Li
,
Jingfeng Peng
,
Hui Feng
,
Yiming Yang
,
Jianbo Gao
,
Chunrui Liu
,
Jie Xu
,
Yanru Zhao
,
Siyu Pan
,
Yixiao Wang
,
Luhong Xu
,
Wenhao Qian
,
Jing Zong
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3390/cells11213393
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3390/cells11213393
Aims: Krüppel-like Factor 9 (KLF9) is a transcription factor that regulates multiple disease processes. Studies have focused on the role of KLF9 in the redox system. In this study, we aimed to explore the effect of KLF9 on diabetic cardiomyopathy. Methods and Results: Cardiac-specific overexpression or silencing of KLF9 in C57BL/6 J mice was induced with an adeno-associated virus 9 (AAV9) delivery system. Mice were also subjected to streptozotocin injection to establish a diabetic cardiomyopathy model. In addition, neonatal rat cardiomyocytes were used to assess the possible role of KLF9 in vitro by incubation with KLF9 adenovirus or small interfering RNA against KLF9. To clarify the involvement of peroxisome proliferator-activated receptors (PPARγ), mice were subjected to GW9662 injection to inhibit PPARγ. KLF9 was upregulated in the hearts of mice with diabetic cardiomyopathy and in cardiomyocytes. In addition, KLF9 overexpression in the heart deteriorated cardiac function and aggravated hypertrophic fibrosis, the inflammatory response and oxidative stress in mice with diabetic cardiomyopathy. Conversely, cardiac-specific silencing of KLF9 ameliorated cardiac dysfunction and alleviated hypertrophy, fibrosis, the cardiac inflammatory response and oxidative stress. In vitro, KLF9 silencing in cardiomyocytes enhanced inflammatory cytokine release and oxidative stress; KLF9 overexpression increased these detrimental responses. Moreover, KLF9 was found to regulate the transcription of PPARγ, which suppressed the expression and nuclear translocation of nuclear Factor E2-related Factor 2 (NRF2). In mice injected with a PPARγ inhibitor, the protective effects of KLF9 knockdown on diabetic cardiomyopathy were counteracted by GW9662 injection. Conclusions: KLF9 aggravates cardiac dysfunction, the inflammatory response and oxidative stress in mice with diabetic cardiomyopathy. KLF9 may become a therapeutic target for diabetic cardiomyopathy.
Related Topics
Concepts
Diabetic cardiomyopathy
Gene knockdown
Oxidative stress
Medicine
Gene silencing
Streptozotocin
Transcription factor
Endocrinology
Pharmacology
Peroxisome proliferator-activated receptor
Internal medicine
Fibrosis
Downregulation and upregulation
Cardiomyopathy
Diabetes mellitus
Biology
Receptor
Heart failure
Apoptosis
Biochemistry
Gene
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/cells11213393
- https://www.mdpi.com/2073-4409/11/21/3393/pdf?version=1666867422
- OA Status
- gold
- Cited By
- 27
- References
- 26
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4307434361
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4307434361Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/cells11213393Digital Object Identifier
- Title
-
KLF9 Aggravates Streptozotocin-Induced Diabetic Cardiomyopathy by Inhibiting PPARγ/NRF2 SignallingWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-10-27Full publication date if available
- Authors
-
Fangfang Li, Jingfeng Peng, Hui Feng, Yiming Yang, Jianbo Gao, Chunrui Liu, Jie Xu, Yanru Zhao, Siyu Pan, Yixiao Wang, Luhong Xu, Wenhao Qian, Jing ZongList of authors in order
- Landing page
-
https://doi.org/10.3390/cells11213393Publisher landing page
- PDF URL
-
https://www.mdpi.com/2073-4409/11/21/3393/pdf?version=1666867422Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/2073-4409/11/21/3393/pdf?version=1666867422Direct OA link when available
- Concepts
-
Diabetic cardiomyopathy, Gene knockdown, Oxidative stress, Medicine, Gene silencing, Streptozotocin, Transcription factor, Endocrinology, Pharmacology, Peroxisome proliferator-activated receptor, Internal medicine, Fibrosis, Downregulation and upregulation, Cardiomyopathy, Diabetes mellitus, Biology, Receptor, Heart failure, Apoptosis, Biochemistry, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
27Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 13, 2024: 9, 2023: 5Per-year citation counts (last 5 years)
- References (count)
-
26Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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