EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA TYPE-II RECEPTOR IN RATLUNG IS REGULATED DURING DEVELOPMENT

Transforming growth factor-beta (TGF-beta) is an autocrine/paracrine g rowth factor that regulates cell proliferation, differentiation, extra cellular ma matrix production and various other cell functions in the lung. TGF-beta exerts its effects on cells by binding to transmembrane heteromeric serine-threonine kinase receptors. The expression and loc alization of specific TGF-beta receptors in the lung, however, have no t yet been investigated. In the present studies, we isolated a 1,762-b ase pair cDNA containing the full-length coding sequence for TGF-beta type II receptor (T beta RII) from rat fetal lung with the use of poly merase chain reaction methods. The expression of T beta RII during lun g development was examined by Northern analysis. A 5.1-kilobase T beta RII mRNA was detected in rat lung tissue. T beta RII mRNA was express ed in rat fetal lung tissue early in development, increased as develop ment proceeded, reached maximal concentration postnatally, and then de creased to the adult level. The localization of T beta RII in fetal an d postnatal rat lung tissue was investigated with the use of in situ h ybridization performed with an antisense RNA probe. T beta RII gene wa s expressed in the mesenchymal tissue and in the epithelial lining of the developing airway at day 16 of gestation. The hybridization signal of T beta RII mRNA was also observed in the adventitial layer of smal l blood vessels. Expression of T beta RII gene in the developing airwa y epithelium occurred along a proximal-distal gradient. In postnatal l ung, T beta RII mRNA was detected mainly in parenchymal tissues and bl ood vessels. Expression of T beta RII remained high in the interstitiu m of interalveolar septa. These data provide direct evidence that T be ta RII is regulated during lung development. The temporal and spatial distribution of T beta RII mRNA in rat lung tissues suggests that TGF- beta plays a role as a multifunctional regulator of epithelial-mesench ymal interactions during lung development.