Journal of Dental Research, Vol 77, 1504-1514, Copyright © 1998 by International & American Associations for Dental Research Online Journals
Changes in the expression of extracellular matrix (ECM) and matrix metalloproteinases (MMP) of proliferating rat parotid acinar cells
R. L. Broverman, K. H. Nguyen, A. da Silveira, L. L. Brinkley, S. P. Macauley, T. Zeng, H. Yamamoto, R. W. Tarnuzzer, G. S. Schultz, M. Kerr and M. G. Humphreys-Beher
Department of Oral Biology, University of Florida Health Science Center, Gainesville 32610, USA.
Tissue morphogenesis, development, and maintenance of function are mediated
by signals generated through the composition of the extracellular matrix.
The regulation of the composition of matrix is determined by enzymes
specific for their degradation, the matrix metalloproteinases. Chronic
injections of the beta-adrenergic receptor agonist, isoproterenol, result
in a non-neoplastic hypertrophy and hyperplasia of the rat parotid gland.
The activity of matrix metalloproteinases, as measured by gelatin
zymography and enzymatic digestion of Azocoll substrates by gland lysates,
decreased significantly (P < 0.05) following 24 hrs of agonist
treatment, and slowly recovered to control values by 6 days of treatment.
Daily administration of the broad-spectrum matrix metalloproteinase
inhibitor Galardin for 3 days in combination with isoproterenol resulted in
enhanced gland hypertrophy compared with that produced by isoproterenol
alone. Given alone, Galardin also caused hypertrophy. The relative
abundance of mRNA for the extracellular matrix molecules, collagens I and
III and fibronectin, declined rapidly following the initiation of
beta-agonist treatment in vivo, while laminin B1 and B2 mRNA levels
increased initially before declining below control levels. These changes in
patterns of mRNA levels also were observed in the concentrations of
glandular protein when Western dot blot analysis of collagens I and III and
laminin, respectively, was used. The importance of laminin, in vivo, was
demonstrated by coinjection of anti-laminin antibody along with
isoproterenol, which resulted in the inhibition of beta-agonist-induced
parotid gland hypertrophy and hyperplasia. These data suggest that
modulation of the ECM is associated with isoproterenol-induced salivary
gland hypertrophy and hyperplasia. It is likely that this modulation of the
ECM takes place through transcriptional regulation of some ECM genes and
regulation of matrix-degrading enzyme activity.
