The significant role of microRNAs (miRNAs) in stem cell development has been expansively discussed in recent publications and they are noticed to be involved in post transcriptional regulation of gene expression by its affinity towards the 3′UTR of target mRNA. Since the expression of miR-21 was high in cells that were derived from MSCs, recent evidence indicates that miR-21 plays a vital role in mesenchymal stem cells (MSCs) differentiation. Despite the fact that miR-21 can be considered as a powerful biomarker for MSCs differentiation, the number of studies related to the above scenario is very limited. This review highlights the recent publications related to the importance of miR-21 specifically in differentiation of MSCs.

Multiple sclerosis (MS) is a widespread neurological autoimmune disease that includes episodes of demyelination in the central nervous system (CNS). The accumulated evidence has suggested that aryl hydrocarbon receptor (Ahr), a ligand-activated transcription factor, is a promising treatment target for MS. Thus, the current study aimed to identify a novel Ahr ligand with anti-inflammatory potential in experimental autoimmune encephalomyelitis (EAE). An in silico analysis was carried out to predict interactions between Ahr and potential natural ligands. The effects of a predicted interaction were examined in vitro using CD4⁺ T cells under T helper17 (Th17) cell-polarizing conditions and lipopolysaccharide (LPS)-stimulated macrophages. Silencing Ahr and microRNA (miR)-132 was achieved by electroporation. Myelin oligodendrocyte glycoprotein (MOG)_35-55 and the adoptive transfer of encephalitogenic CD4⁺ T cells were used to induce EAE. Molecular docking analysis and in vitro data identified gallic acid (GA) as a novel Ahr ligand with potent activation potential. GA induced the expression of Ahr downstream genes, including cytochrome P450 family 1 subfamily A member 1 (Cyp1a1) and the miR-212/132 cluster, and promoted the formation of the Ahr/Ahr nuclear translocator (Arnt) complex. In vivo, GA-treated mice were resistant to EAE and exhibited reduced levels of proinflammatory cytokines and increased levels of transforming growth factor-β (TGF-β). Furthermore, GA reduced infiltration of CD4⁺CD45⁺ T cells and monocytes into the CNS. The anti-inflammatory effects of GA were concomitant with miR-132-potentiated cholinergic anti-inflammation and the regulation of the pathogenic potential of astrocytes and microglia. Inducing EAE by adoptive transfer revealed that CD4⁺ T cells were not entirely responsible for the ameliorative effects of GA. Our findings identify GA as a novel Ahr ligand and provide molecular mechanisms elucidating the ameliorative effects of GA on EAE, suggesting that GA is a potential therapeutic agent to control inflammation in autoimmune diseases such as MS.