Tang Guan-Nan The First Affiliated Hospital
Li Cheng-Lin The First Affiliated Hospital
Yao Yin The First Affiliated Hospital and Huazhong University of Science and Technology
Xu Zhi-Bin The First Affiliated Hospital
Deng Meng-Xia The First Affiliated Hospital
Wang Shu-Yue The First Affiliated Hospital
Sun Yue-Qi The First Affiliated Hospital
Shi Jian-Bo The First Affiliated Hospital
Fu Qing-Ling The First Affiliated Hospital
Regulating the Function of Specific miRNAs Could Represent a New Approach to Asthma Therapy
Allergic airway diseases have become a significant global public health concern and threatened patients' quality of life while also causing substantial medical and financial burdens . Airway hyperreactivity, mucus hypersecretion, and reversible airway obstructions are the hallmarks of allergic airway inflammation . Allergic rhinitis and asthma share several common features, such as high serum IgE levels, increased cellular infiltration, and excessive T helper type 2 (Th2) activation [3,4]. Th2 cytokines, such as interleukin 4 (IL-4), IL-5, and IL-13, could affect asthma immunomodulatory properties . Insufficient regulatory T-cell (Treg) suppression is responsible for the excessive Th2 response in allergic airway diseases .
Recently, microRNAs (miRNAs) were reported to contribute to the progress of allergic airway inflammation. miRNAs are endogenous short noncoding RNAs that predominantly silence target genes by binding to their 3′ untranslated regions (UTRs) to prevent translation or induce degradation . A number of studies have confirmed the critical roles of miRNAs in a series of biological processes, including immune regulation . Many miRNAs were reported to be differentially expressed and play important roles in allergic airway inflammation, and miRNA-let-7, miRNA-155, and miRNA-126 have been studied most frequently. The miRNA-let-7-inhibited IL-13 expression and knockdown of the let-7 miRNA family inhibited both cytokine production and disease pathology in animal asthma models [9,10]. miRNA-155-deficient mice were found to be immunodeficient and displayed increased airway remodeling . Targeting miRNAs, such as miR-126, in the airways may lead to anti-inflammatory treatments for allergic asthma . Therefore, regulating the functions of miRNAs is a novel target for treating allergic diseases.
Mesenchymal stem cells (MSCs) are multipotent cells that are capable of differentiation into three mesenchymal cell types. Increasing evidence in animal studies and preliminary clinical trials has demonstrated that MSCs not only possess multipotent differentiation potential but also exhibit strong immunomodulation potential. Initial clinical trials have been completed or are underway with regard to inflammatory bowel disease, systemic lupus erythematosus (SLE), organ transplantation, acute respiratory distress syndrome, and acute kidney injury [13,14]. It has been conceived that bone marrow-derived mesenchymal stem cells (BM-MSCs) could suppress allergen-specific Th2 cell responses and, therefore, prevent allergic airway inflammation [15–17].
Human BM-MSCs have no or limited immunogenicity, and allogeneic human BM-MSCs are well tolerated and therapeutically active in rodent models without no rejection response [18,19]. Consequently, we and other groups reported that human-derived BM-MSCs have successfully activated the immunomodulation to alleviate the allergic inflammation in mice model [17,19]. However, the mechanisms underlying the immune regulation have still not been well documented, especially regarding the correlation between BM-MSCs and miRNAs. Currently, very few articles reported the complex roles of BM-MSCs and miRNAs in allergic responses. Only one report observed that human BM-MSCs suppress stretch-induced MiR-155 and cytokines in cultured human bronchial epithelial cells . There are no studies that refer to the correlation between miRNA and the treatment of BM-MSCs in airway allergic inflammation.
In this study, we analyzed aberrant miRNAs and key immune regulators in a mouse asthma model with or without BM-MSCs treatment using both miRNA and messenger RNA (mRNA) PCR arrays. We identified a series of differently expressed miRNAs and protein-coding genes as key regulator candidates after the induction of allergic inflammation and BM-MSCs treatment. We further confirmed the key miRNA–target gene axis to mediate the asthma pathogenesis and BM-MSCs therapy.
Stem Cells and Development, published by Mary Ann Liebert, Inc., is globally recognized as the trusted source for critical, even controversial coverage of emerging hypotheses and novel findings. With a focus on stem cells of all tissue types and their potential therapeutic applications, the Journal provides clinical, basic, and translational scientists with cutting-edge research and findings.The above article was first published in the June 2016 issue of Stem Cells and Development with the title “MicroRNAs Involved in Asthma After Mesenchymal Stem Cells Treatment”. The views expressed here are those of the authors and are not necessarily those of Stem Cells and Development, Mary Ann Liebert, Inc., publishers, or their affiliates. No endorsement of any entity or technology is implied.