Early postnatal dexamethasone influences matrix metalloproteinase-2 and -9, and their tissue inhibitors in the developing rat lung.
In order to test the hypothesis that early postnatal exposure to dexamethasone (Dex) influences matrix metalloproteinases (MMP)-2 and -9, as well as their tissue inhibitors (TIMP-1 and -2) in the developing rat lung, newborn rats (3 litters/group) were treated with low Dex (0.1 mg/kg/day, IM), high Dex (0.5 mg/kg/day), or equivalent volumes of saline at 5 days postnatal age (P5), P6, and P7. Lung weight and lung MMP and TIMP levels were determined at sacrifice (7 days postinjection, P14; at weaning, P21; and at adolescence, P45, n = 10/group and time). Dex did not adversely affect lung weight or lung MMP-2 levels, which peaked in all groups at P21 and then fell by P45. In contrast, Dex decreased TIMP-2 at all time intervals, but achieved statistical significance only at P45. An imbalance in MMP-2/TIMP-2 ratio was noted at P21, with elevations occurring in the low and high Dex-treated groups. Lung MMP-9 levels remained comparable with controls during low Dex treatment. However, high Dex exposure resulted in elevated lung MMP-9 levels at P21 and P45. Lung TIMP-1 levels increased only with high Dex exposure at P14 and P21, whereas the lung MMP-9/TIMP-1 ratio was elevated at P21 in the high Dex group, and at P45 in both Dex-treated groups. These data provide evidence that early postnatal dexamethasone results in an imbalance between gelatinase-A and -B, and their tissue inhibitors in the developing rat lung. These changes may be responsible, in part, for some of the known maturational effects of steroids on lung structure in the newborn.
Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of California, Irvine Medical Center, Orange, California, USA.
Arwin M
AM
Valencia
Kay D
KD
Beharry
Jorge G
JG
Ang
Kamakshi
K
Devarajan
Richard
R
Van Woerkom
Maria
M
Abrantes
Kenji
K
Nishihara
Eileen
E
Chang
Joshua
J
Waltzman
Houchang D
HD
Modanlou
D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry / Q000201:enzymology* / Q000254:growth & development / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D003907:Dexamethasone; D020778:Matrix Metalloproteinase 2