An increase in hyaluronan by lung fibroblasts: A biomarker for intensity and activity of interstitial pulmonary fibrosis?

The purpose of the present study was to clarify the roles of hyaluronan (HA) production of lung fibroblasts in the pathogenesis of pulmonary fibrosis. Quantitative and comparative assessments of the HA levels in bronchoalveolar lavage fluid (BALF) and lung fibroblast-conditioned media (F-CM) were made at various stages during the development of bleomycin-induced pulmonary fibrosis in rats. In bleomycin-treated animals, the HA levels in F-CM increased significantly (P < 0.01) on day 1 after bleomycin treatment, peaked on day 3, and then gradually declined and returned to control values on days 14-28. The HA concentrations of BALF in the bleomycin group were significantly increased (P < 0.01) on day 3, were maximal on day 7, and thereafter gradually decreased, remaining significantly above normal values (P < 0.01) on day 14, but returning to control values by day 28. In the bleomycin group, the HA levels both in BALF and in F-CM were significantly correlated with the cell components in BALF and there was a significant correlation between the HA concentration in BALF and in the F-CM. Lung fibroblasts were activated and produced increased HA which resulted in excessive accumulation of HA in the lung in the early stage of pulmonary fibrosis; the increased HA synthesis of lung fibroblasts and enhanced HA concentrations of BALF might reflect the intensity of alveolitis and the disease activity.