Vol. 278, Issue 4, L737-L743, April 2000
Cloning and expression of guinea pig TIMP-2. Expression in
normal and hyperoxic lung injury
Jorge
Meléndez1,
Vilma
Maldonado1,
Collin D.
Bingle2,
Moisés
Selman3, and
Annie
Pardo4
1 Instituto Nacional de Cancerología,
Mexico DF 14000; 3 Instituto Nacional de
Enfermedades Respiratorias, Mexico DF 14080;
4 Facultad de Ciencias, Universidad Nacional
Autónoma de México, Mexico DF 04510, Mexico; and
2 University of Sheffields, Sheffields S10 2RX
United Kingdom
Tissue
inhibitors of metalloproteinases (TIMPs) play a key regulatory role in
extracellular matrix remodeling. By screening a lung library with a
human TIMP-2 cDNA probe, we have isolated the cDNA corresponding to
guinea pig TIMP-2. The 3.5-kb cDNA presents an open reading frame that
predicts a protein of 220 amino acids showing 97.2, 96.8, 97.2, and
77.3% overall identity with human, mouse, rat, and chicken TIMP-2,
respectively. Guinea pig TIMP-2 cDNA was expressed in CHO-K1 cells,
showing a protein with the expected molecular weight and activity.
Northern blot analysis revealed TIMP-2 expression in brain, kidney,
intestine, spleen, heart, and lung. Transforming growth factor-
downregulated TIMP-2 mRNA in guinea pig lung fibroblasts, whereas a
variety of other stimuli showed no effect. In normal and
hyperoxia-exposed lungs, TIMP-2 mRNA was mainly localized in alveolar
macrophages and epithelial cells. No quantitative differences were
found by Northern blot. These results confirm that TIMP-2 is highly
conserved in mammals and largely expressed in lungs.
tissue inhibitor of metalloproteinase-2; matrix metalloproteinase; hyperoxia
