MicroRNAs (miRNAs) are small non-coding RNAs that can repress protein synthesis by translational repression and mRNA decay to regulate signaling pathways. miRNAs play important roles in various cellular processes including cell inflammatory response and differentiation.

NF-κB is one of the best-characterized transcription factors providing the link between early membrane-proximal signaling events and changes in gene expression, and regulates the expression of many genes that play a role in inflammation. Here, we evaluated the in vitro effect of lipopolysaccharide (LPS) on cultured bovine alveolar macrophages and report that miR-26b, a LPS - responsive miRNA, repressed the phosphatase and tensin homolog (PTEN) involved in the activation of the NF-κB signaling pathway in bovine alveolar macrophages. LPS stimulation up-regulated miR-26b after 1 h and down-regulated miR-26b after 6 and 36 h. Furthermore, miR-26b enhanced the LPS-induced TNF-α, IL-8, IL-1β, IL-10 and nitric oxide production and directly inhibited that of IL-6. In addition, miR-26b promoted LPS-induced NF-B signaling pathway. Moreover, miR-26b directly leads to PTEN silencing in bovine alveolar macrophages. PTEN silencing enhanced the LPS-induced mRNA expression of TNF-α, IL-8, IL-1β, IL-10 and IL-6, and up-regulated the NF-κB pathway. Taken together, we conclude that miR-26b participates in the inflammatory response of LPS- stimulated bovine alveolar macrophages by modulating the NF-κB pathway through targeting PTEN.

The efficacy of the current protocols to differentiate mouse induced pluripotent stem cells (iPSCs) and Mesenchymal Stem Cells (MSCs) into alveolar epithelial type II (AEC II) cells is low. And, whether miRNAs are involved in the differentiation of iPSCs and MSCs into lung epithelial cells is unknown. We aimed to identify specific miRNAs that can efficiently promote the differentiation of iPSCs and MSC into AEC II cells. Through miRNA microarray analysis, we identified that miR-29a was highly enriched in AEC II cells. miR-29a induced the differentiation of iPSCs and MSCs into AEC II cells under the stimulation of proper growth factors and growing on appropriate matrix. We show here that miR-29a suppressed the Dual-Specificity Phosphatase 2 (DUSP2) involved in the activation of the mitogen-activated protein kinase (MAPK) signaling pathway to promote the differentiation of iPSCs and MSCs into AEC II cells. In addition, dexamethasone, 8-bromoadenosine 3, 5-cyclic monophosphate (cAMP), and isobutylmethylxanthine (IBMX) (DCI) further facilitated the miR-29a-mediated differentiation process. Moreover, we found that AEC II cells derived from iPSCs and MSCs secreted pulmonary surfactant and trans-differentiated into alveolar epithelial type I (AEC I) cells. Furthermore, miR-29a engineered MSC-AEC II cells attenuated lung injury induced by elastase. In addition, our studies may contribute to the cell-based therapy for COPD.