Forkhead box transcription factor 1: role in the pathogenesis of diabetic cardiomyopathy

Kandula, Vidya; Kosuru, Ramoji; Li, Haobo; Yan, Dan; Zhu, Qiqi; Lian, Qingquan; Ge, Ren‐Shan; Xia, Zhengyuan; Irwin, Michael G.

doi:10.1186/s12933-016-0361-1

Cited by 89 publications

(69 citation statements)

References 138 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, it was found that miRNAs mediated the benefits of exercise and bariatric surgery to the heart in diabetic/prediabetic patients, and the decreased circulating miR-21 were restored after bariatric surgery or physical activity [25, 29]. Moreover, upregulation of miR-21 or downregulation of its targets could lead to diabetic cardiac dysfunction [30–32]. Therefore, miR-21 might play important roles in diabetic cardiomyopathy, and it may be a new therapeutic target for metabolic diseases such as T2DM and obesity.…”

Section: Introductionmentioning

confidence: 99%

MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin

Dai

Fan

et al. 2018

Cardiovasc Diabetol

View full text Add to dashboard Cite

BackgroundDiabetes is a leading cause of mortality and morbidity across the world. Over 50% of deaths among diabetic patients are caused by cardiovascular diseases. Cardiac diastolic dysfunction is one of the key early signs of diabetic cardiomyopathy, which often occurs before systolic dysfunction. However, no drug is currently licensed for its treatment.MethodsType 9 adeno-associated virus combined with cardiac Troponin T promoter were employed to manipulate miR-21 expression in the leptin receptor-deficient (db/db) mice. Cardiac structure and functions were measured by echocardiography and hemodynamic examinations. Primary cardiomyocytes and cardiomyocyte cell lines were used to perform gain/loss-of-function assays in vitro.ResultsWe observed a significant reduction of miR-21 in the diastolic dysfunctional heart of db/db mice. Remarkably, delivery of miR-21 efficiently protected against the early impairment in cardiac diastolic dysfunction, represented by decreased ROS production, increased bioavailable NO and relieved diabetes-induced cardiomyocyte hypertrophy in db/db mice. Through bioinformatic analysis and Ago2 co-immunoprecipitation, we identified that miR-21 directly targeted gelsolin, a member of the actin-binding proteins, which acted as a transcriptional cofactor in signal transduction. Moreover, down-regulation of gelsolin by siRNA also attenuated the early phase of diabetic cardiomyopathy.ConclusionOur findings reveal a new role of miR-21 in attenuating diabetic cardiomyopathy by targeting gelsolin, and provide a molecular basis for developing a miRNA-based therapy against diabetic cardiomyopathy.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0767-z) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin

Dai

Fan

et al. 2018

Cardiovasc Diabetol

View full text Add to dashboard Cite

show abstract

“…Loss of FoxO transcription factors can protect against microglial cell demise during oxidative stress (57) and Aβ exposure (58), promotes the protective effects of metabotropic glutamate receptors (59), increases neuronal cell survival through nicotinamide adenine dinucleotide (NAD + ) precursors (60), enhances survival with growth factors (61), such as erythropoietin (EPO) (30, 40, 43, 62) and neurotrophins (63–65), and can lessen metabolic and vascular disease (66). Work has suggested that some antipsychotics, such as clozapine, may function through FoxO inhibition to protect against apoptotic neuronal cell loss (67).…”

Section: Foxo Transcription Factors and Cell Deathmentioning

confidence: 99%

Forkhead Transcription Factors: Formulating a FOXO Target for Cognitive Loss

Maiese¹

2018

CNR

View full text Add to dashboard Cite

show abstract

“…Inhibition or loss of FoxO activity usually improves cell survival during apoptotic cell injury. Blockade of FoxO transcription factor activity can protect against microglial cell demise during oxidative stress (71) and Aβ exposure (208), foster the protective effects of metabotropic glutamate receptors (209), increase neuronal cell survival through nicotinamide adenine dinucleotide (NAD + ) precursors (210), raise survival with growth factors (211), such as erythropoietin (EPO) (150, 212–214) and neurotrophins (215–217), and lessen metabolic and vascular disease (218). Antipsychotics, such as clozapine, may function through FoxO inhibition to protect against apoptotic neuronal cell loss (219).…”

Section: Foxo Transcription Factorsmentioning

confidence: 99%

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

Maiese¹

2018

CNR

View full text Add to dashboard Cite

BACKGROUND With the global increase in life span expectancy, neurodegenerative disorders continue to affect an ever increasing number of individuals throughout the world. New treatment strategies for neurodegenerative diseases are desperately required given the lack of current treatment modalities. METHODS Here we examine novel strategies for neurodegenerative disorders that include circadian clock genes, non-coding ribonucleic acids (RNAs), and the mammalian forkhead transcription factors of the O class (FoxOs). RESULTS Circadian clock genes, non-coding RNAs, and FoxOs offer exciting prospects to potentially limit or remove the significant disability and death associated with neurodegenerative disorders. Each of these pathways have an intimate relationship with the programmed death pathways of autophagy and apoptosis and share a common link to the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) and the mechanistic target of rapamycin (mTOR). Circadian clock genes are necessary to modulate autophagy, limit cognitive loss, and prevent neuronal injury. Non-coding RNAs can control neuronal stem cell development and neuronal differentiation and offer protection against vascular disease such as atherosclerosis. FoxOs provide exciting prospects to block neuronal apoptotic death and to activate pathways of autophagy to remove toxic accumulations in neurons that can lead to neurodegenerative disorders. CONCLUSIONS Continued work with circadian clock genes, non-coding RNAs, and FoxOs can offer new prospects and hope for the development of vital strategies for the treatment of neurodegenerative diseases. These innovative investigative avenues have the potential to significantly limit disability and death from these devastating disorders.

show abstract

Forkhead box transcription factor 1: role in the pathogenesis of diabetic cardiomyopathy

Cited by 89 publications

References 138 publications

MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin

MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin

Forkhead Transcription Factors: Formulating a FOXO Target for Cognitive Loss

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

Contact Info

Product

Resources

About