Anti-inflammatory effects of miRNA-146a induced in adipose and periodontal tissues

Taiki Sanada,Tomomi Sano,Yusuke Sotomaru,Rehab Alshargabi,Yosuke Yamawaki,Akiko Yamashita,Hiroaki Matsunaga,Misaki Iwashita,Takanori Shinjo,Takashi Kanematsu,Tomoichiro Asano,Fusanori Nishimura

doi:10.1016/j.bbrep.2020.100757

Abstract

MicroRNA (miRNA) plays an important role in diverse cellular biological processes such as inflammatory response, differentiation and proliferation, and carcinogenesis. miR-146a has been suggested as a negative regulator of the inflammatory reaction. Although, it has been reported as expressed in inflamed adipose and periodontal tissues, however, miR-146a's inhibitory effects against inflammatory response in both the tissues, are not well understood. Therefore, in this study, the inhibitory effects of miR-146a on both adipose and periodontal inflammation, was investigated. In vitro study has revealed that miR-146a transfection into either adipocytes or gingival fibroblasts, has resulted in a reduced cytokine gene expression, observed on co-culturing the cells with macrophages in the presence of lipopolysaccharides (LPS), in comparison to the control miRNA transfected. Similarly, miR-146a transfection into macrophages resulted in a reduced expression of TNF-α gene and protein in response to LPS stimulation. In vivo study revealed that a continuous intravenous miR-146a administration into mice via tail vein, protected the mice from developing high-fat diet-induced obesity and the inflammatory cytokine gene expression was down-regulated in both adipose and periodontal tissues. miR-146a appeared to be induced by macrophage-derived inflammatory signals such as TNF-α by negative feed-back mechanism, and it suppressed inflammatory reaction in both adipose and periodontal tissues. Therefore, miR-146a could be suggested as a potential therapeutic molecule and as a common inflammatory regulator for both obesity-induced diabetes and related periodontal diseases.

Highlights

Obesity is a multifactorial chronic disorder, wherein, disease onset is greatly influenced by genetic and environmental factors [1]
The results indicated that LPS stimulation for 24 h, resulted in significantly increased miR-146a expression in the adipocytes (Fig. 1B), gingival fibroblasts (Fig. 1C), and macrophages (Fig. 1D)
Discussion miR-146a was noted to be expressed in the inflamed adipose and periodontal tissues, and in the adipocytes and gingival fibroblasts, by macrophage-derived supernatants under inflammatory stimuli. miR146a transfection resulted in decreased inflammatory cytokine gene expression in both, adipocytes and fibroblasts. miR-146a has been reported to suppress IRAK1 or TRAF6, expressions, both of which are signaling molecules, known to mediate tumor necrosis factor-α (TNF-α) signals

Summary

Introduction

Obesity is a multifactorial chronic disorder, wherein, disease onset is greatly influenced by genetic and environmental factors [1]. It further up-regulates the risk of developing various life-threatening chronic diseases such as cancer and coronary heart diseases. Obesity appears to influence the systemic energy metabolism and inflammatory responses, evokes low-grade inflammatory status throughout the body, and exacerbates periodontal inflammation as well [2]. Adipose tissue-derived inflammatory response such as increased tumor necrosis factor-α (TNF-α) production is suggested to exacerbate the systemic low-grade inflammation, which further act as a deteriorating factor for other inflammatory diseases such as periodontal disease and inflammation. When up-regulated, it is suggested to, in turn influence adipose tissue inflammation which may further lower insulin sensitivity [5]

Methods

Results

Conclusion