Cloning and regulation of the rat activin beta(E) subunit

Using a combination of polymerase chain reaction (PCR) procedures, we have cloned and sequenced the rat activin beta(E) subunit cDNA. The putative pro tein corresponding to the prepro-activin beta(E) subunit was predicted to c omprise 350 amino acids which, when cleaved between amino acid residues 236 and 237, would yield a mature polypeptide of approximately M-r 12 500 with a predicted pI of 5.1. Two cDNA transcripts for activin beta(E) were ident ified; these differed by 738 bp in the 3'-untranslated region. Activin beta (E) mRNA transcripts were expressed only in rat liver and lung tissue as as sessed by Northern blotting and PCR analysis. Relatively higher levels of b oth transcripts were found in the liver, whereas the lung contained lower l evels that were detectable by PCR only. In situ hybridisation data showed t hat, within the liver, activin beta(E) mRNA was localised to hepatocytes. I n vivo treatment with lipopolysaccharide as a means of activating the immun e system and the hepatic acute-phase response resulted in stimulated activi n beta(E) mRNA levels, compared with untreated, control rats. This increase d expression was accompanied by a preferential increase in the amount of th e long activin beta(E) transcript over the shorter transcript. These findin gs suggested that the two activin beta(E) mRNA transcripts may be products of alternative splicing events or use alternative polyadenylation sites whi ch are differentially regulated during in inflammation. These data provide evidence of a role for activin beta(E) in liver function and inflammation i n the rat.