Expression of matrix metalloproteinases 2, 7 and 9, and their tissue inhibitors 1 and 2, in developing rabbit tracheae.

Abstract

Background: Structural changes in the developing conducting airway impact the rigidity of the airway, altering the airway's ability to sustain its shape during ventilation. The developmental changes in airway compliance oppose the changes in compliance of the developing lung; thus the expression profiles of matrix modeling proteins likely are also opposite in these developing organs.

Objectives: To determine the profiles of matrix metalloproteinases (MMPs) -2, -7, and -9 and tissue inhibitors (TIMPs) -1 and -2 in the developing trachea and test the hypothesis these profiles would contrast those previously reported for the lung.

Methods: Rabbits tracheae were harvested at 21 days of gestation, 3 and 17 days postgestation and at adulthood. Tissue homogenates were analyzed by substrate zymography for the activity of MMPs, and reverse zymography for TIMPs. Immunostainings on neonatal lamb tracheal rings were used to localize MMP-2 and 9.

Results: Analysis revealed an age-dependent decrease in total MMP-2 quantity and the ratio of active to latent forms. TIMP-2 shows a time-dependent increase throughout airway development. Total MMP-9 and TIMP-1 quantities were unchanged across these ages, although MMP-9 protein was found predominantly in its latent form during development and predominantly in its active form during adulthood. Respiratory epithelial cells reacted positive for both MMP-2 and 9 and trachealis muscle fibers were positive for MMP-2. No MMP-7 expression was identified in the rabbit airway.

Conclusions: The opposing developmental patterns in MMP-2 expression between the airway and lung lead to speculation regarding the role of MMP-2 activity on changes in organ compliance.