DIFFERENTIAL EFFECTS OF MICRORNA-21, 99 AND 145 ON LUNG REGENERATION BY PUTATIVE STEM CELLS DURING RECOVERY FROM INFLUENZA PNEUMONIA

Abstract

Currently, two populations of putative stem cells following influenza pneumonia are identified - “proliferating alveolar type II cells” and “distal airway stem cells”, although their roles are still unclear. Moreover, microRNAs (miRNAs) are known to be implicated during regenerative process. This study thus aims to describe the spatial and temporal roles of these pulmonary cells, and provide insights on their relationships with expression of three specific miRNAs (miR-21, miR-99a and miR-145) during lung regeneration. Through an in-vivo sub-lethal influenza pneumonia mouse model, the data suggested proliferating AT2 cells to be the major stem cells involved in early lung regeneration. Down-regulation of miR-21 resulted in severe morbidity, followed by miR-99a and miR-145. In conclusion, there is a complex interplay between specific miRNA expression, lung regeneration and inflammation during influenza pneumonia recovery. Inhibited expression of miR-21 and miR-99a (but not miR-145) can lead to deleterious effects in the lungs during influenza pneumonia.