Lin28a protects against diabetic cardiomyopathy via the PKA/ROCK2 pathway

Sun, Siyu; Zhang, Mingming; Lin, Jie; Hu, Jianqiang; Zhang, Rongqing; Li, Congye; Wei, Tianlu; Sun, Dongdong; Wei, Jianqin; Wang, Haichang

doi:10.1016/j.bbrc.2015.11.065

Cited by 19 publications

(18 citation statements)

References 28 publications

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“…Diabetic mice induced by intraperitoneal streptozocin injections were randomized for treatment with lentivirus carrying Lin28a siRNA or Lin28a cDNA to knock down or overexpress Lin28a, respectively. Lin28a overexpression significantly decreased RhoA/ROCK signaling to alleviate mitochondria cristae destruction and promote heart function in diabetic mice (Sun et al, 2016). Additionally, Dkk1 adenovirus is transduced by intramyocardial injection, and Dkk1 overexpression aggravates Dox-induced CM apoptosis via the mitochondrial damage pathway (Liang et al, 2019).…”

Section: Gene Editing For Genetic Disordermentioning

confidence: 99%

Mechanotranduction Pathways in the Regulation of Mitochondrial Homeostasis in Cardiomyocytes

Liao

Yan

et al. 2021

Front. Cell Dev. Biol.

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Mitochondria are one of the most important organelles in cardiomyocytes. Mitochondrial homeostasis is necessary for the maintenance of normal heart function. Mitochondria perform four major biological processes in cardiomyocytes: mitochondrial dynamics, metabolic regulation, Ca2+ handling, and redox generation. Additionally, the cardiovascular system is quite sensitive in responding to changes in mechanical stress from internal and external environments. Several mechanotransduction pathways are involved in regulating the physiological and pathophysiological status of cardiomyocytes. Typically, the extracellular matrix generates a stress-loading gradient, which can be sensed by sensors located in cellular membranes, including biophysical and biochemical sensors. In subsequent stages, stress stimulation would regulate the transcription of mitochondrial related genes through intracellular transduction pathways. Emerging evidence reveals that mechanotransduction pathways have greatly impacted the regulation of mitochondrial homeostasis. Excessive mechanical stress loading contributes to impairing mitochondrial function, leading to cardiac disorder. Therefore, the concept of restoring mitochondrial function by shutting down the excessive mechanotransduction pathways is a promising therapeutic strategy for cardiovascular diseases. Recently, viral and non-viral protocols have shown potentials in application of gene therapy. This review examines the biological process of mechanotransduction pathways in regulating mitochondrial function in response to mechanical stress during the development of cardiomyopathy and heart failure. We also summarize gene therapy delivery protocols to explore treatments based on mechanical stress–induced mitochondrial dysfunction, to provide new integrative insights into cardiovascular diseases.

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Section: Gene Editing For Genetic Disordermentioning

confidence: 99%

Mechanotranduction Pathways in the Regulation of Mitochondrial Homeostasis in Cardiomyocytes

Liao

Yan

et al. 2021

Front. Cell Dev. Biol.

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“…For example, transient (30 min) treatment with nitrite induced PKA activation, leading to mitochondrial fusion and cytoprotection through phosphorylation of Drp1 at Ser655 [225]. Most recently, Lin28-induced inhibition of apoptosis in a diabetic cardiomyopathy model was shown to be abolished by pretreatment with a PKA inhibitor H89 [226]. These findings suggest that the role of PKA in apoptosis regulation is context dependent.…”

Section: Pkamentioning

confidence: 99%

Signaling Pathways in Cardiac Myocyte Apoptosis

Xia

Liu

Cheng

2016

BioMed Research International

138

132

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Cardiovascular diseases, the number 1 cause of death worldwide, are frequently associated with apoptotic death of cardiac myocytes. Since cardiomyocyte apoptosis is a highly regulated process, pharmacological intervention of apoptosis pathways may represent a promising therapeutic strategy for a number of cardiovascular diseases and disorders including myocardial infarction, ischemia/reperfusion injury, chemotherapy cardiotoxicity, and end-stage heart failure. Despite rapid growth of our knowledge in apoptosis signaling pathways, a clinically applicable treatment targeting this cellular process is currently unavailable. To help identify potential innovative directions for future research, it is necessary to have a full understanding of the apoptotic pathways currently known to be functional in cardiac myocytes. Here, we summarize recent progress in the regulation of cardiomyocyte apoptosis by multiple signaling molecules and pathways, with a focus on the involvement of these pathways in the pathogenesis of heart disease. In addition, we provide an update regarding bench to bedside translation of this knowledge and discuss unanswered questions that need further investigation.

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“…In support of its role in diabetic hearts, LIN28 overexpression alleviates mitochondrial dysfunction and cardiomyocyte apoptosis preventing cardiomyopathy in T1D mice (Sun et al, ). LIN28 depletion exacerbates cardiac symptoms in diabetic mice (Sun et al, ; Zhang et al, ). These studies support a critical role for LIN28 in diabetic heart and kidney disease.…”

Section: Rbps Implicated In Diabetesmentioning

confidence: 99%

Emerging roles of RNA‐binding proteins in diabetes and their therapeutic potential in diabetic complications

Nutter

Kuyumcu‐Martinez

2017

WIREs RNA

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Diabetes is a debilitating health care problem affecting 422 million people around the world. Diabetic patients suffer from multisystemic complications that can cause mortality and morbidity. Recent advancements in high-throughput next-generation RNA-sequencing and computational algorithms led to the discovery of aberrant posttranscriptional gene regulatory programs in diabetes. However, very little is known about how these regulatory programs are mis-regulated in diabetes. RNA-binding proteins (RBPs) are important regulators of posttranscriptional RNA networks, which are also dysregulated in diabetes. Human genetic studies provide new evidence that polymorphisms and mutations in RBPs are linked to diabetes. Therefore, we will discuss the emerging roles of RBPs in abnormal posttranscriptional gene expression in diabetes. Questions that will be addressed are: Which posttranscriptional mechanisms are disrupted in diabetes? Which RBPs are responsible for such changes under diabetic conditions? How are RBPs altered in diabetes? How does dysregulation of RBPs contribute to diabetes? Can we target RBPs using RNA-based methods to restore gene expression profiles in diabetic patients? Studying the evolving roles of RBPs in diabetes is critical not only for a comprehensive understanding of diabetes pathogenesis but also to design RNA-based therapeutic approaches for diabetic complications. WIREs RNA 2018, 9:e1459. doi: 10.1002/wrna.1459 This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > Splicing Regulation/Alternative Splicing Translation > Translation Regulation.

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Lin28a protects against diabetic cardiomyopathy via the PKA/ROCK2 pathway

Cited by 19 publications

References 28 publications

Mechanotranduction Pathways in the Regulation of Mitochondrial Homeostasis in Cardiomyocytes

Mechanotranduction Pathways in the Regulation of Mitochondrial Homeostasis in Cardiomyocytes

Signaling Pathways in Cardiac Myocyte Apoptosis

Emerging roles of RNA‐binding proteins in diabetes and their therapeutic potential in diabetic complications

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