Transferrin gene expression and transferrin immunolocalization in developing foetal rat lung.

In previous studies we have shown that transferrin (Tf) specifically stimulates dermatan- and chondroitin-sulphate proteoglycan accumulation around lung cells, and in the extracellular matrix of lung tissue, in vitro. The aim of this study was to determine whether the gene for Tf was activated in specific lung cells during development, and whether the protein product showed evidence of association with extracellular matrix. The expression of the gene in developing lung was shown by the hybridization of a Tf cDNA to a 2.4 kb (kilobase) mRNA species in total RNA extracts of foetal lung. The expression of the Tf gene in comparison to a control gene (GAPD, glyceraldehyde phosphate dehydrogenase) was greatest in 19, 20 and 21 day foetal lung, rising from low levels on day 18 and decreasing markedly at term (day 22). Extracts of RNA from primary cultures of mesenchymal fibroblasts and type II epithelial cells were also analysed for Tf mRNA. These experiments indicated that Tf gene expression was predominantly confined to the mesenchymal compartment. The presence of Tf in histological sections of foetal lung was demonstrated by immunohistochemistry and showed a distinct pattern, with intense staining of the alveolar and the capillary basement membranes. The matrix surrounding the mesenchymal fibroblasts was stained in a diffuse network while epithelial cells were unstained. The staining was low from days 12-16 of gestation, increased to a maximum at days 19-20 but decreased markedly toward term. The Tf staining did not co-localize with transferrin receptor, also demonstrated by immunohistochemistry. These results suggest that Tf is not only present at specific sites in the developing lung, but also is synthesized according to a strict developmental schedule of gene expression.