Tissue inhibitor of metalloproteinase-1 mRNA is specifically induced in lung tissue after birth.
Interactions between extracellular matrix, proteins, metalloproteinases, and their inhibitors play a major role in determining the structure of the lung during in utero development and after birth. To better understand the molecular mechanisms underlying lung development and morphogenesis, expression of the tissue inhibitor of metalloproteinase (TIMP-1) gene was examined 1) through the course of late fetal development, 2) when normal fetal development was interrupted by premature birth and extrauterine survival, and 3) during exposure of prematurely delivered neonates to hyperoxia. Total RNA isolated from lung tissue of fetal baboons (Papio sp) at 140, 150, and 180 d of gestation (term gestation = 180 d); baboons prematurely delivered at 140 d of gestation, 1, 2, 6, and 10 d old; and premature baboons ventilated for 6 and 10 d with 100% oxygen was examined by Northern blot analysis. The results demonstrated that TIMP-1 mRNA, which is expressed at low levels during fetal development, undergoes a marked increase in abundance shortly after both premature and term birth. This parturition-induced pattern of gene expression appears to be tissue specific to the lung and, contrary to results reported for adult and neonatal animals, is not affected by ventilation of the premature lungs with 100% inspired oxygen. Although the physiologic consequences of TIMP-1 mRNA induction by birth are not yet known, these data suggest a possible role for TIMP-1 in postnatal adaptation of lung tissue.
Minoo
P
P
Southwest Foundation for Biomedical Research, San Antonio, Texas 78284.
Penn
R
R
deLemos
D M
DM
Coalson
J J
JJ
deLemos
R A
RA
D000818:Animals; D000831:Animals, Newborn; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D005333:Fetus / Q000378:metabolism; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics*; D007743:Labor, Obstetric; D008168:Lung / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D010100:Oxygen; D010215:Papio; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics*; D014018:Tissue Distribution; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D008666:Metalloendopeptidases; D010100:Oxygen