DIFFERENTIAL EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA RECEPTORS IN RAT-KIDNEY DEVELOPMENT

Transforming growth factor-beta 1 (TGF-beta 1) is strongly expressed d uring embryogenesis and in sites undergoing intense development and mo rphogenesis. Two receptor serine/threonine kinases (types I and II) ha ve been identified as signal-transducing TGF-beta receptors. This stud y was undertaken to further explore the role of the distinct TGF-beta receptors during kidney development. The species-specific sequence inf ormation for the two T beta R-I, namely, activin receptor-like kinase- 5 (ALK-5) and Tsk7L, in the rat was sought. Two full-length T beta R-I cDNAs were cloned from a neonatal rat kidney and lung libraries, and sequencing revealed that they were the rat homologs of human ALK-5 and murine Tsk7L. Both types I and II TGF-beta receptors are expressed in the kidney as determined by Northern blot analysis. T beta R-II mRNA abundance was significantly greater in the neonatal rat kidney compare d with the adult rat kidney. Similarly, ALK-5 mRNA was more highly exp ressed in the fetal and neonatal rat kidney than the adult rat kidney. In contrast, there was no significant difference in Tsk7L mRNA abunda nce among the fetal, neonatal, and adult rat kidney. Thus, based on th ese findings, both T beta R-II and ALK-5 are developmentally regulated in the kidney. Increased expression of T beta R-II and ALK-5 proteins in the developing kidney was confirmed by immunohistochemistry. Inter estingly, the two TGF-beta receptors did not entirely colocalize, rais ing the intriguing possibility that other TGF-beta signaling receptors may be involved.