2006 Volume 31 Issue 4 Pages 345-355
Although paraquat (PQ) is known to induce pulmonary fibrosis, how it does so is not entirely clear. To elucidate the mechanisms involved, the profile of gene expression in the lung at three months after exposure to PQ (7 mg/kg, s.c., daily for eight administrations) was investigated in rats using a DNA microarray. Changes in gene expression that were considered to reflect damage to the lung, a change in the balance of electrolytes and fluid, and alveolar remodeling were observed. The products of these genes were: CSF-1 receptor, which is a receptor of inflammatory cytokines that activates monocyte/macrophages; TGF-beta type II receptor, which is a receptor of TGF-betas involved in wound healing and fibrosis; a subunit of Na+/K+-ATPase, an amiloride-sensitive cation channel, and a subunit of the potassium channel, all of which regulate the alveolar fluid balance and play a role in clearing lung edema; the adenosine A2a receptor, which has a protective function in the lung and interacts with dopamine D1 and D2 receptors to regulate the function of amiloride-sensitive cation channels; cofilin, which is involved in the depolymerization and cleavage of actin filaments; LIM motif-containing protein kinase 1, which negatively regulates the activity of cofilin; SHPS-1, which regulates the integrin-mediated reorganization of the cytoskeleton; and sodium channel beta 2, which is involved in cell adhesion and migration. These results indicate that PQ-induced pulmonary fibrosis does not merely terminate as cicatrices three months after the discontinuation of PQ treatment, but that dynamic functional change continues in the lung.
