Immunomodulatory or immunosuppressive properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) facilitate the treatment of acute respiratory distress syndrome and acute lung injury (ALI). Dysregulated miRNA (miRNA or miR) expression associated with the effects of BM-MSCs was assessed in a rat model of lipopolysaccharide (LPS)-induced ALI. The present study performed biochemical tests to assess five analytes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate, blood urea nitrogen (BUN), and creatinine (CREA). Total cell count was assessed and the percentage of bronchoalveolar lavage neutrophil content was also examined. The results Histopathological examination of rat upper lobe lung tissue was then used to estimate lung injury score (LIS). The levels of AST, lactate, BUN and creatinine (excluding ALT), released into the circulation upon injury, were significantly lower in ALI rats treated with BM-MSCs than in ALI rats alone (P<0.05). BM-MSC rats exhibited a significantly decreased bronchoalveolar lavage neutrophil percentage and LIS compared with that of LPS treated rats alone (P<0.05). In addition, the miRNA expression profile was determined following treatment with BM-MSCs via microarray analysis. A total of 95/690 miRNAs were differentially expressed following the treatment of BM-MSCs in rats with ALI. Among the 95 miRNAs, 66 were upregulated and 29 were downregulated; 9 miRNAs were significantly upregulated (miR-1843-3p, miR-323-3p, miR-183-5p, miR-182 and miR-196b-3p) or downregulated (miR-547-3p, miR-301b-5p, miR-503-3p and miR-142-3p). A total of 3 miRNAs were inversely expressed in ALI treated with BM-MSCs compared with untreated ALI. Of these 3 miRNAs, the expression of miR-142-3p and miR-503-3p was upregulated in the LPS groups and downregulated in the BM-MSC groups. miR-196b-3p was downregulated in the LPS group and upregulated in the BM-MSC groups. miRNAs have a role in cell proliferation, immune response, inflammation and apoptosis, which may be associated with the therapeutic effects of BM-MSCs in ALI. In summary, BM-MSCs improved multi-organ damage and attenuated lung injury. Different miRNA profiles were expressed following BM-MSC treatment of ALI. These dysregulated miRNAs participated in BM-MSC-mediated immunomodulation of ALI.
We investigated the expression profiles of miRNAs in acute lung injury (ALI) rats after hypother mia treatment. ALI rats were induced with lipopoly saccharide (LPS) and maintained with hypothermia (HT) or normothermia (NT) for 6 hours. HT attenuated inflammatory cell infiltration in the lung and improved biochemical indicators of multi-organ dysfunction. Nineteen miRNAs were significantly differentially ex pressed in the HT group compared with the nT group. miR-142, miR-98, miR-541, miR-503, miR-653, miR-223, miR-323 and miR-196b exhibited opposite pat terns of expression between the two groups. These dysregulated miRNAs were mainly involved in the immune and inflammatory response on functional an notation analyses. This study shows that HT has lung protective effects and influences expression profiles of miRNAs in ALI. And dysregulated miRNAs after HT modulate the immune and inflammation in ALI. These results suggest that dysregulated miRNAs play a role in the mechanism of the lung protective effects of HT in ali.
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