The association between microRNA-21 and hypertension-induced cardiac remodeling

Watanabe, Ken; Narumi, Takatsune; Watanabe, Tetsu; Otaki, Yoichiro; Takahashi, Toshio; Aono, Tomonori; Goto, Jun; Toshima, Taku; Sugai, Takayuki; Wanezaki, Masahiro; Kutsuzawa, Daisuke; Kato, Shigehiko; Tamura, H.; Nishiyama, Satoshi; Takahashi, Hitomi; Arimoto, Takanori; Shishido, Tetsuro; Watanabe, Masafumi

doi:10.1371/journal.pone.0226053

Cited by 36 publications

(27 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to this, positive miR-21 feedback has also been observed in Ang-II -mediated ERK/TGF-β/Smad signaling [ 35 , 67 ]. miR-21 have been reported in patients with aortic stenosis, hypertrophic cardiomyopathy and dilated cardiomyopathy [ 35 , 68 ]. In contrast, miR-132 reduces TGF-β expression after cardiac ischemia [ 69 ].…”

Section: Signaling Pathways Related To Cardiac Fibrosismentioning

confidence: 99%

Mesenchymal Stem Cells Therapies on Fibrotic Heart Diseases

Gubert

Vasques

et al. 2021

IJMS

View full text Add to dashboard Cite

Stem cell therapy is a promising alternative approach to heart diseases. The most prevalent source of multipotent stem cells, usually called somatic or adult stem cells (mesenchymal stromal/stem cells, MSCs) used in clinical trials is bone marrow (BM-MSCs), adipose tissue (AT-MSCs), umbilical cord (UC-MSCs) and placenta. Therapeutic use of MSCs in cardiovascular diseases is based on the benefits in reducing cardiac fibrosis and inflammation that compose the cardiac remodeling responsible for the maintenance of normal function, something which may end up causing progressive and irreversible dysfunction. Many factors lead to cardiac fibrosis and failure, and an effective therapy is lacking to reverse or attenuate this condition. Different approaches have been shown to be promising in surpassing the poor survival of transplanted cells in cardiac tissue to provide cardioprotection and prevent cardiac remodeling. This review includes the description of pre-clinical and clinical investigation of the therapeutic potential of MSCs in improving ventricular dysfunction consequent to diverse cardiac diseases.

show abstract

Section: Signaling Pathways Related To Cardiac Fibrosismentioning

confidence: 99%

Mesenchymal Stem Cells Therapies on Fibrotic Heart Diseases

Gubert

Vasques

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…TGF-β1 contributes to cardiac fibrosis development through SMAD-dependent and SMAD-independent pathways. TGF-β1 generally exerts its biological effects by activating downstream mediators, including SMAD2 and SMAD3, while negatively regulated by SMAD7 expression [ 147 , 148 , 149 ]. SMADs have been reported to play a pivotal role in the transcription of ECM proteins [ 150 ].…”

Section: Cardiac Fibrosis and Hect-type E3 Ligasementioning

confidence: 99%

The Role of HECT-Type E3 Ligase in the Development of Cardiac Disease

Goto

Otaki

Watanabe

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Despite advances in medicine, cardiac disease remains an increasing health problem associated with a high mortality rate. Maladaptive cardiac remodeling, such as cardiac hypertrophy and fibrosis, is a risk factor for heart failure; therefore, it is critical to identify new therapeutic targets. Failing heart is reported to be associated with hyper-ubiquitylation and impairment of the ubiquitin–proteasome system, indicating an importance of ubiquitylation in the development of cardiac disease. Ubiquitylation is a post-translational modification that plays a pivotal role in protein function and degradation. In 1995, homologous to E6AP C-terminus (HECT) type E3 ligases were discovered. E3 ligases are key enzymes in ubiquitylation and are classified into three families: really interesting new genes (RING), HECT, and RING-between-RINGs (RBRs). Moreover, 28 HECT-type E3 ligases have been identified in human beings. It is well conserved in evolution and is characterized by the direct attachment of ubiquitin to substrates. HECT-type E3 ligase is reported to be involved in a wide range of human diseases and health. The role of HECT-type E3 ligases in the development of cardiac diseases has been uncovered in the last decade. There are only a few review articles summarizing recent advancements regarding HECT-type E3 ligase in the field of cardiac disease. This study focused on cardiac remodeling and described the role of HECT-type E3 ligases in the development of cardiac disease. Moreover, this study revealed that the current knowledge could be exploited for the development of new clinical therapies.

show abstract

“…Some basal phosphorylation seemed to be present in the absence of LPS stimulation with both antibodies. All three antibodies -the single phospho-specific as well as the double phosphospecific ones -have repeatedly been used in the literature [38][39][40]. This issue will be followed up in the discussion section.…”

Section: Lps-mediated Signalling In Mmscsmentioning

confidence: 99%

The inflammatory signalling mediator TAK1 mediates lymphocyte recruitment to lipopolysaccharide-activated murine mesenchymal stem cells through interleukin-6

et al. 2021

View full text Add to dashboard Cite

As a response to pro-inflammatory signals mesenchymal stem cells (MSCs) secrete agents and factors leading to lymphocyte recruitment, counteracting inflammation, and stimulating immunosuppression. On a molecular level, the signalling mediator TGF-β-activated kinase 1 (TAK1) is activated by many pro-inflammatory signals, plays a critical role in inflammation and regulates innate and adaptive immune responses as well. While the role of TAK1 as a signalling factor promoting inflammation is well documented, we also considered a role for TAK1 in anti-inflammatory actions exerted by activated MSCs. We, therefore, investigated the capacity of lipopolysaccharide (LPS)-treated murine MSCs with lentivirally modulated TAK1 expression levels to recruit lymphocytes. TAK1 downregulated by lentiviral vectors expressing TAK1 shRNA in murine MSCs interfered with the capacity of murine MSCs to chemoattract lymphocytes, indeed. Analysing a pool of 84 secreted factors we found that among 26 secreted cytokines/factors TAK1 regulated expression of one cytokine in LPS-activated murine MSCs in particular: interleukin-6 (IL-6). IL-6 in LPS-treated MSCs was responsible for lymphocyte recruitment as substantiated by neutralizing antibodies. Our studies, therefore, suggest that in LPS-treated murine MSCs the inflammatory signalling mediator TAK1 may exert anti-inflammatory properties via IL-6.

show abstract

The association between microRNA-21 and hypertension-induced cardiac remodeling

Cited by 36 publications

References 51 publications

Mesenchymal Stem Cells Therapies on Fibrotic Heart Diseases

Mesenchymal Stem Cells Therapies on Fibrotic Heart Diseases

The Role of HECT-Type E3 Ligase in the Development of Cardiac Disease

The inflammatory signalling mediator TAK1 mediates lymphocyte recruitment to lipopolysaccharide-activated murine mesenchymal stem cells through interleukin-6

Contact Info

Product

Resources

About