Emerging Role of mTOR Signaling‐Related miRNAs in Cardiovascular Diseases

Samidurai, Arun; Kukreja, Rakesh C.; Das, Anindita

doi:10.1155/2018/6141902

Cited by 38 publications

(35 citation statements)

References 346 publications

(396 reference statements)

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“…mTOR is also associated with various diseases including various cancers (40, 41) such as prostate cancer (42), kidney cancer (43), and breast cancer (44) due to mutations and misregulations in the mTOR pathway. It is also associated with other diseases including cardiovascular disease (45), renal diseases (46), pulmonary fibrosis (47), and diabetes mellitus (48). Associations of mTOR signalling pathway with normal and abnormal brain, neurite development, synapse formation and associated functions have been discussed in detail.…”

Section: Mtor - the Signalling Hubmentioning

confidence: 99%

mTOR signalling pathway - A root cause for idiopathic autism?

et al. 2019

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Autism spectrum disorder (ASD) is a complex neurodevelopmental monogenic disorder with a strong genetic influence. Idiopathic autism could be defined as a type of autism that does not have a specific causative agent. Among signalling cascades, mTOR signalling pathway plays a pivotal role not only in cell cycle, but also in protein synthesis and regulation of brain homeostasis in ASD patients. The present review highlights, underlying mechanism of mTOR and its role in altered signalling cascades as a triggering factor in the onset of idiopathic autism. Further, this review discusses how distorted mTOR signalling pathway stimulates truncated translation in neuronal cells and leads to downregulation of protein synthesis at dendritic spines of the brain. This review concludes by suggesting downstream regulators such as p70S6K, eIF4B, eIF4E of mTOR signalling pathway as promising therapeutic targets for idiopathic autistic individuals.

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Section: Mtor - the Signalling Hubmentioning

confidence: 99%

mTOR signalling pathway - A root cause for idiopathic autism?

et al. 2019

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“…miRNAs are small non-coding RNAs that regulate gene expression by binding to the 3'UTR of their target genes in a sequence-specific manner, thereby decreasing the gene expression [43]. miRNAs have been demonstrated to play crucial roles in most biological and physiological processes, including cell growth and differentiation, metabolism, immunity, cancer, and autoimmune disorders [44][45][46]. Recently, increasing evidences have suggested that miRNAs are associated with M1 macrophage polarization, such as miR-181a, miR-130a, let-7c, miR-99a [26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

MiR-103 protects from recurrent spontaneous abortion via inhibiting STAT1 mediated M1 macrophage polarization

Zhu¹,

Li²,

Zhang³

et al. 2020

Int. J. Biol. Sci.

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Recurrent spontaneous abortion (RSA) is a common complication of early pregnancy. Excessive M1 macrophage was found to be involved in RSA, but the underlying mechanisms remains unclear. MicroRNAs play critical roles in RSA as well as the polarization of macrophages; however, the regulatory effect of miRNAs on M1 differentiation in RSA has not been fully investigated. In this study, miRNA microarray assay revealed that miR-103 was significantly decreased in RAW264.7-derived M1 macrophages upon IFNγ and LPS stimulation. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that in RSA patients, miR-103 expression was decreased substantially, and negatively correlated with that of STAT1. Moreover, down-regulation of miR-103 could sensitively discriminate RSA patients from normal pregnancies (NP) subjects. Experiments in vitro showed that overexpression of miR-103 suppressed M1 polarization by inhibiting STAT1/IRF1 signaling pathway and vice versa. miR-103 regulated STAT1 expression by direct binding to its 3'-UTR. Moreover, our in vivo study demonstrated that overexpressed miR-103 could reduce mice embryo resorption and M1 polarization effectively. Overall, the results suggested that decreased miR-103 was involved in RSA by increasing M1 macrophage polarization via promoting STAT1/IRF1 signaling pathway. miR-103 may be explored as a promising diagnostic marker and therapeutic target for RSA.

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“…mTOR is a direct negative regulator of autophagy [53]. In vascular smooth muscle cells, autophagy is inhibited by the activated Akt-mTOR signaling pathway [54]. In cardiomyocytes, activated mTOR exerts a protective effect in ischemia/reperfusion injury by restraining autophagy [55].…”

Section: Discussionmentioning

confidence: 99%

Ang II Enhances Atrial Fibroblast Autophagy and Promotes Atrial Remodeling Through the AT1-ERK-mTOR Signaling Pathway

Xu¹,

Chen²,

Qiu³

et al. 2020

Preprint

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Background: Atrial remodeling is a common pathological change in atrial fibrillation (AF), while the mechanism of atrial remodeling remains unclear. In the present study, we investigated the autophagy and collagen secretion in atrial fibroblasts in response to renin-angiotensin system (RAS) activation and elucidated the relationship between atrial fibroblast autophagy and atrial remodeling. Methods: Right atrial tissues was obtained from patients that underwent cardiac valve replacement after signed the informed consent form. In vivo, subcutaneous perfusion of angiotensin II (Ang II) was used to mimic activation of the RAS and induce atrial remodeling. Electrical remodeling and AF induction were assessed by electrophysiology and programmed stimulation. In vitro, atrial fibroblasts were isolated and cultured. Autophagic flux changes were assessed by mCherry‑GFP‑LC3 adenovirus transfection. All samples were collected, collagen expression, autophagy changes and atrial remodeling were evaluated by western blot, masson’s trichrome staining, immunohistochemistry and immunoﬂuorescence mainly.Results: Atrial tissue samples from patients with atrial fibrillation showed more collagen deposition and enhanced autophagy than those with sinus rhythm. Chronic subcutaneous Ang II perfusion in mice promoted atrial remodeling and susceptible to AF induction. In cultured atrial fibroblasts, the expression of collagen I (COL-I) and collagen III (COL-III) and autophagy both increased when cells were treated with Ang II, and the autophagic flux was enhanced by Ang II. However, blocking autophagy reduced the expression of COL-I and COL-III. Besides, Ang II induced the phosphorylation of ERK and suppressed the phosphorylation of mTOR. In contrast, inhibition of the angiotensin II type 1 receptor (AT1) or ERK signaling pathway not only suppressed the autophagy induced by Ang II but also reduced COL-I and COL-III expression. Conclusions: In summary, these results suggest that Ang II promotes autophagy in atrial fibroblasts, which aggravates atrial remodeling and increases the susceptibility to AF induction. Autophagy may be a potential target for relieving atrial remodeling and AF after RAS activation.

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Emerging Role of mTOR Signaling‐Related miRNAs in Cardiovascular Diseases

Cited by 38 publications

References 346 publications

mTOR signalling pathway - A root cause for idiopathic autism?

mTOR signalling pathway - A root cause for idiopathic autism?

MiR-103 protects from recurrent spontaneous abortion via inhibiting STAT1 mediated M1 macrophage polarization

Ang II Enhances Atrial Fibroblast Autophagy and Promotes Atrial Remodeling Through the AT1-ERK-mTOR Signaling Pathway

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