MicroRNA-30a-5p silencing polarizes macrophages toward M2 phenotype to alleviate cardiac injury following viral myocarditis by targeting SOCS1

Abstract

Viral myocarditis (VMC) is a life-threatening disease characterized by severe cardiac inflammation generally caused by coxsackievirus B3 (CVB3) infection. Several microRNAs (miRNAs or miRs) are known to play crucial roles in the pathogenesis of VMC. The study aims to decipher the role of miR-30a-5p in the underlying mechanisms of VMC pathogenesis. We first quantified miR-30a-5p expression in a CVB3-induced mouse VMC model. The physiological characteristics of mouse cardiac tissues were then detected by HE and Picrosirius red staining. We established the correlation between miR-30a-5p and SOCS1 using dual luciferase gene assay and Pearson's correlation coefficient. The expression of inflammatory factors (IFN-γ, IL-6, IL-10 and IL-13), M1 polarization markers (TNF-α, iNOS), M2 polarization markers (Arg-1, IL-10), myocardial hypertrophy markers (ANP and BNP) was detected by RT-qPCR and Western blot analysis. miR-30a-5p was found to be highly expressed in VMC mice. Silencing of miR-30a-5p improved the cardiac function index, reduced heart weight/body weight ratio, myocardial tissue pathological changes and fibrosis degree, serological indexes, as well as pro-inflammatory factor levels, while enhancing anti-inflammatory factor levels in VMC mice. Furthermore, silencing of miR-30a-5p inhibited M1 polarization of macrophages while promoting M2 polarization in vivo and in vitro. SOCS1 was a target gene of miR-30a-5p, and the aforementioned cardioprotective effects of miR-30a-5p silencing were reversed upon silencing of SOCS1. Overall, this study shows that silencing of miR-30a-5p may promote M2 polarization of macrophages and improve cardiac injury following VMC via SOCS1 upregulation, constituting a potential therapeutic target for VMC treatment.

Therapeutic Role of miR‐30a in Lipoteichoic Acid‐Induced Endometritis via Targeting the MyD88/Nox2/ROS Signaling

“…For instance, the ectopic expression of miR-30a suppresses the proliferation and migration and tumorigenesis of gastric cancer cells by directly inhibiting ITGA2 [34].More notably, the immunomodulatory effect of miR-30a has been disclosed in several studies. Silence of miRNA-30a polarizes macrophages toward M2 phenotype to ameliorate cardiac injury through targeting SOCS1 [24]. Moreover, another study clearly showed that the overexpression of miR-30a in monocyte cells significantly attenuates Mycobacterium tuberculosis infection, as well as the secretion of TNF-α, IL-6, and IL-8 [35].…”

“…Our previous study has also shown that upregulation of the miR-92b expression improves the outcome of endometritis in mice via targeting PTEN [17].miR-30a is a highly conserved and multifunctional miRNA and has been demonstrated to be involved in tumor growth and immune response. It was found that miR-30a regulates IRF4 to influence IL-17-associated autoimmune inflammation and also mediates the inflammatory macrophage polarization [24]. In particular, upregulation of miR-30a targets Neurod1 and alleviates the inflammatory responses during injured spinal cord [25].…”

Comparison and Analysis on the Existing Single-Herbal Strategies against Viral Myocarditis

“…Moreover, the elevated M2 macrophage polarization is closely relevant to the inhibition of inflammation and conducive to alleviating VMC [ 79 ]. Adoptive transfer of M2 macrophages lowers cardiac inflammation [ 80 ], while accelerating M2 polarization of macrophages ameliorates cardiac damage following VMC in mice [ 81 ]. With viral infection, acute perimyocarditis leads to haemodynamic instability [ 82 ].…”

MicroRNAs Regulating Renin–Angiotensin–Aldosterone System, Sympathetic Nervous System and Left Ventricular Hypertrophy in Systemic Arterial Hypertension

“…MiR-155 also had increased expression in the plasma of hypertensive patients, and this high expression was associated with inflammatory markers such as interleukin-6 (IL-6) and c-reactive protein [ 65 ]. Other circulating miRNAs also dysregulated in the plasma of hypertensive patients, such as miR-29 and 30a, are overexpressed, whereas miR-133 is downregulated [ 64 ], and these miRNAs are associated with the processes of inflammation and LVH [ 75 , 78 ].…”