Isoproterenol modulates matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor-2 (TIMP-2) in rat parotid gland

Abstract

Objective: Chronic isoproterenol treatment causes hypertrophy and hyperplasia of rodent salivary glands. Cell-extracellular matrix interactions play a critical role in salivary gland proliferation and matrix metalloproteinases (MMPs) are known to be involved in cell proliferation. The present study was undertaken to investigate the expression of MMP-2 and the tissue inhibitor metalloproteinase (TIMP)-2 in rat parotid gland following isoproterenol treatment.

Design: Female Wistar rats were daily treated with isoproterenol (25mg/kg body weight) for 0, 1, 3, and 7 days. Expression of parotid gland MMP-2 and its tissue inhibitor TIMP-2 was analysed by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry.

Results: Our results suggest that isoproterenol modulates expression of MMP-2 and TIMP-2 mRNAs, as well as their protein expression levels in a time dependent-manner. Interestingly, at day 1 of treatment, MMP-2 and TIMP-2 expression were higher in comparison to untreated gland. At days 3 and 7, we can observe a gradual decrease of mRNA and protein levels of MMP-2 and TIMP-2.

Conclusions: Our results suggest the presence of a isoproterenol-dependent modulation of extracellular matrix components. Such a modulation seems to be associated with β-adrenergic agonist-induced hyperplasy, occurring during the first 24h of agonist treatment, and hypertrophy of the parotid gland.