miR‐222 inhibits cardiac fibrosis in diabetic mice heart via regulating Wnt/β‐catenin‐mediated endothelium to mesenchymal transition

Wang, Zheng; Wang, Zhongmin; Xiao, Lili; Yao, Rui; Du, Binbin; Li, Yapeng; Wu, Leiming; Liang, Cui; Huang, Zhen; Li, Pengcheng; Zhang, Yanzhou

doi:10.1002/jcp.29119

Cited by 28 publications

(22 citation statements)

References 39 publications

(52 reference statements)

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“…On the other hand, the anti-fibrotic role of miRNA-221/222 family has been confirmed, as their down-regulation was associated with heart failure ( Verjans et al, 2018 ). The interplay between Wnt and miR-222 in EndMT regulation has been recently suggested ( Wang et al, 2020 ); specifically, miR-222 is able to suppress the hyperglycemia-induced EndMT and inhibit cardiac fibrosis by negatively regulating the Wnt/β-catenin pathway in diabetic mice ( Wang et al, 2020 ). Lastly, a further protective effect versus EndMT is exerted through the notch pathway and involves miR-18a-5p ( Geng and Guan, 2017 ).…”

Section: Mirnas Regulation Of Dcm-associated Endmtmentioning

confidence: 99%

EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress

Giordo

Ahmed

Allam

et al. 2021

Front. Cell Dev. Biol.

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Diabetes-associated complications, such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis, the main consequences of long-term hyperglycemia, often lead to organ dysfunction, disability, and increased mortality. A common denominator of these complications is the myofibroblast-driven excessive deposition of extracellular matrix proteins. Although fibroblast appears to be the primary source of myofibroblasts, other cells, including endothelial cells, can generate myofibroblasts through a process known as endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their typical phenotype to acquire mesenchymal features, characterized by the development of invasive and migratory abilities as well as the expression of typical mesenchymal products such as α-smooth muscle actin and type I collagen. EndMT is involved in many chronic and fibrotic diseases and appears to be regulated by complex molecular mechanisms and different signaling pathways. Recent evidence suggests that small RNAs, in particular microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are crucial mediators of EndMT. Furthermore, EndMT and miRNAs are both affected by oxidative stress, another key player in the pathophysiology of diabetic fibrotic complications. In this review, we provide an overview of the primary redox signals underpinning the diabetic-associated fibrotic process. Then, we discuss the current knowledge on the role of small RNAs in the regulation of EndMT in diabetic retinopathy, nephropathy, cardiomyopathy, and atherosclerosis and highlight potential links between oxidative stress and the dyad small RNAs-EndMT in driving these pathological states.

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Section: Mirnas Regulation Of Dcm-associated Endmtmentioning

confidence: 99%

EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress

Giordo

Ahmed

Allam

et al. 2021

Front. Cell Dev. Biol.

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“…Myocardial hypertrophy and fibrosis are among the most representative changes in DCM [25,26]. In DCM, the dynamic balance between synthesis and deposition of the myocardial extracellular matrix is disturbed, and excessive deposition of collagen and an imbalance in the collagen ratio lead to cardiac remodeling [27][28][29]. BNP is among the most relevant molecular markers of cardiac hypertrophy [30], and the level of BNP increased in the DCM group.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Huangqi Shengmai Yin on Type 1 Diabetes-Induced Cardiomyopathy by Improving Myocardial Lipid Metabolism

Cao

Pan

Sui

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Diabetic cardiomyopathy (DCM) is one of the many complications of diabetes. DCM leads to cardiac insufficiency and myocardial remodeling and is the main cause of death in diabetic patients. Abnormal lipid metabolism plays an important role in the occurrence and development of DCM. Huangqi Shengmai Yin (HSY) has previously been shown to alleviate signs of heart disease. Here, we investigated whether HSY could improve cardiomyopathy caused by type 1 diabetes mellitus (T1DM) and improve abnormal lipid metabolism in the diabetic heart. Streptozotocin (STZ) was used to establish the T1DM mouse model, and T1DM mice were subsequently treated with HSY for eight weeks. The changes in the cardiac conduction system, histopathology, blood myocardial injury indices, and lipid content and expression of proteins related to lipid metabolism were evaluated. Our results showed that HSY could improve electrocardiogram; decrease the serum levels of CK-MB, LDH, and BNP; alleviate histopathological changes in cardiac tissue; and decrease myocardial lipid content in T1DM mice. These results indicate that HSY has a protective effect against T1DM-induced myocardial injury in mice and that this effect may be related to the improvement in myocardial lipid metabolism.

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“…Cardiac function can be improved by inhibiting EndMT (46). Multiple studies have found that attenuated EndMT can reduce cardiac fibrosis (11,20,(47)(48)(49)(50)(51). EndMT can also cause vascular endothelial dysfunction and serves an important role in the process of atherosclerosis (52,53) and pulmonary fibrosis (54)(55)(56).…”

Section: Discussionmentioning

confidence: 99%

Activation of activin/Smad2 and 3 signaling pathway and the potential involvement of endothelial‑mesenchymal transition in the valvular damage due to rheumatic heart disease

Xian

Chen

et al. 2020

Mol Med Rep

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Rheumatic heart disease (RHD) is an autoimmune disease caused by rheumatic fever following group A hemolytic streptococcal infection and primarily affects the mitral valve. RHD is currently a major global health problem. However, the exact pathological mechanisms associated with RHD-induced cardiac valve damage remain to be elucidated. The endothelial-mesenchymal transition (EndMT) serves a key role in a number of diseases with an important role in cardiac fibrosis and the activin/Smad2 and 3 signaling pathway is involved in regulating the EndMT. Nevertheless, there are no studies to date, to the best of the authors' knowledge, investigating the association between RHD and EndMT. Thus, the aim of the current study was to investigate the potential role of EndMT in cardiac valve damage and assess whether activin/Smad2 and 3 signaling was activated during RHD-induced valvular injury in a rat model of RHD induced by inactivated Group A streptococci and complete Freund's adjuvant. Inflammation and fibrosis were assessed by hematoxylin and eosin and Sirius red staining. Serum cytokine and rheumatoid factor levels were measured using ELISA kits. Expression levels of activin/Smad2 and 3 signaling pathway-related factors [activin A, Smad2, Smad3, phosphorylated (p-)Smad2 and p-Smad3], EndMT-related factors [lymphoid enhancer factor-1 (LEF-1), Snail1, TWIST, zinc finger E-box-binding homeobox (ZEB)1, ZEB2, α smooth muscle actin (α-SMA) and type I collagen α 1 (COL1A1)], apoptosis-related markers (BAX and cleaved caspase-3) and valvular inflammation markers (NF-κB and p-NF-κB) were detected using reverse transcription-quantitative PCR and western blot analyses. Compared with the control group, the degree of valvular inflammation and fibrosis, serum levels of IL-6, IL-17, TNF-α and expression of apoptosis-related markers (BAX and cleaved caspase-3) and valvular inflammation marker (p-NF-κB), activin/Smad2 and 3 signaling pathway-related factors (activin A, p-Smad2 and p-Smad3), EndMT-related factors (LEF-1, Snail1, TWIST, ZEB 1, ZEB2, α-SMA and COL1A1) were significantly increased in the RHD group. These results suggested that the activin/Smad2 and 3 signaling pathway was activated during the development of valvular damage caused by RHD and that the EndMT is involved in RHD-induced cardiac valve damage.

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miR‐222 inhibits cardiac fibrosis in diabetic mice heart via regulating Wnt/β‐catenin‐mediated endothelium to mesenchymal transition

Cited by 28 publications

References 39 publications

EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress

EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress

Protective Effects of Huangqi Shengmai Yin on Type 1 Diabetes-Induced Cardiomyopathy by Improving Myocardial Lipid Metabolism

Activation of activin/Smad2 and 3 signaling pathway and the potential involvement of endothelial‑mesenchymal transition in the valvular damage due to rheumatic heart disease

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miR‐222 inhibits cardiac fibrosis in diabetic mice heart via regulating Wnt/β‐catenin‐mediated endothelium to mesenchymal transition

Cited by 28 publications

References 39 publications

EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress

EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress

Protective Effects of Huangqi Shengmai Yin on Type 1 Diabetes-Induced Cardiomyopathy by Improving Myocardial Lipid Metabolism

Activation of activin/Smad2 and 3 signaling pathway and the&nbsp;potential involvement of endothelial‑mesenchymal transition in the valvular damage due to rheumatic heart disease

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Activation of activin/Smad2 and 3 signaling pathway and the potential involvement of endothelial‑mesenchymal transition in the valvular damage due to rheumatic heart disease