Basic study to develop a new therapeutic drug in chronic obstructive pulmonary disease

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To develop a new therapeutic way in chronic obstructive pulmonary disease, we have studied the regulatory mechanisms of various functions in lung epithelial cells. The findings in this study were summarized below.1)Sp1, Sp3 and ETS transcription factors regulate transdifferentiation from alveolar type II to type I epithelial cells. Sp1 increased type I cell-specific gene expression, and Sp3 competitively inhibited the effect of Sp1. In addition, the activity of ETS transcription factor, MEF, was controlled by protein kinase C.2)Lipopolysaccaride changed subcellualr sidtribution of aquaporin-5, a water channel protein in alveolar type I cells, from intracellular vesicle compartment to plasma membrane, which is mediated by p38 MAP kinase.3)Glucocorticoid is the most effective to treat the lung inflammation, but severe adverse effects of glucocorticoid restricts its chronic use. We found that glycyrrhizin (GL) has glucocorticoid-like transcriptional regulatory effect the without activating glucocorticoid receptor, using in vitro reporter gene assay. The glucocorticoid-like effect of GL was confirmed in several in vivo studies, GL strongly inhibited lung inflammation as well as glucocorticoid, but did not decrease body weight and thymus volume.