Elastase release of basic fibroblast growth factor in pulmonary fibroblast cultures results in down-regulation of elastin gene transcription. A role for basic fibroblast growth factor in regulating lung repair.
We have reported previously that a factor released by elastase treatment of pulmonary fibroblast cultures is capable of down-regulating elastin gene expression. In the present study we have pursued the identification of the factor released by elastase treatment and the characterization of the level of elastin gene expression at which this factor exerts its effect. We have found by immunologic and biochemical procedures that elastase treatment results in the release of basic fibroblast growth factor (bFGF) that is bound within the matrix. Both purified bFGF and bFGF released by elastase from cell matrices decrease the transcriptional level of the elastin gene by 70-80% within 24 h. Transient transfections of pulmonary fibroblasts with a series of elastin promoter deletion constructs show that the region of the elastin gene responsive to bFGF is located within sequences spanning -900 to -200 base pairs. The biological implications of these findings coupled with our previous report are significant, since they demonstrate that elastase digestion of pulmonary fibroblast matrices not only results in the proteolysis of elastin but also results in the release of a potent regulator of elastin gene transcription whose activity can influence repair mechanisms.
Rich
C B
CB
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Nugent
M A
MA
Stone
P
P
Foster
J A
JA
D000818:Animals; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004549:Elastin / Q000096:biosynthesis* / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000302:isolation & purification / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic
D010446:Peptide Fragments; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D004549:Elastin; D015500:Chloramphenicol O-Acetyltransferase; D010196:Pancreatic Elastase