Identification, cloning, and developmental expression of hepatoma-derived growth factor in the developing rat heart

Hepatoma derived growth factor (HDGF) was identified as a developmentally regulated cardiac gene by mRNA differential display using 12-day rat fetal conotruncus vs. newborn aorta. The full-length rat HDGF cDNA was cloned from a rat fetal heart cDNA library and found to be 94 and 88% homologous to the mouse and human sequence, respectively. The rat sequence, like the human and mouse, contains a highly conserved amino portion and putative bipartite nuclear localization sequence. By Northern analysis, HDGF is highly expressed in the fetal conotruncus, heart, kidney, brain, and gut. By immunocytochemistry, HDGF was first detected only in atrial myocytes, hind gut epithelia, and notochord of the E10 rat with a nuclear expression pattern. By E12, expression had broadened to include the ventricular myocytes, endocardial cells, and cells of the ventricular outflow tract. HDGF is unique in that it is the first described nuclear targeted growth factor in the developing heart. The early expression of HDGF in embryonic heart and fetal gut suggests that HDGF may play a role in cardiovascular growth and differentiation.