AML1-LIKE TRANSCRIPTION FACTOR INDUCES SERINE ELASTASE ACTIVITY IN-OVINE PULMONARY-ARTERY SMOOTH-MUSCLE CELLS

In previous studies, we showed that induction of pulmonary artery (PA) smooth muscle cell (SMC) elastase activity by serum-treated elastin ( STE) requires DNA transcription. We therefore used differential mRNA d isplay to identify transcripts expressed coincident with elastase indu ction. Twenty-four individual transcripts were differentially expresse d from a screen of approximate to 2000 mRNA sequences. An mRNA with se quence homology to the human transcription factor AML1 was identified and subsequently cloned from ovine PA SMCs. Since AML1 binds to a cons ensus sequence in the promoter of neutrophil elastase, we pursued the possibility that AML1 is a candidate transcription factor for SMC elas tase. We documented by immunohistochemistry that serum stimulation ind uces increased expression of AML1 in the nucleus of PA SMCs. We also s howed that STE induction of elastase activity is associated with early expression of AML1 mRNA and protein and that AML1 consensus sequence DNA binding activity is increased in nuclear extracts of STE-treated c ells. In addition, AML1 antisense oligonucleotides reduced serum induc tion of elastase activity. Our study thus provides the first functiona l evidence of AML1 transcriptional activity related to elastase genes and offers novel insights into the broader biological significance of AML1 in nonmyeloid cells.