The Effect Of MMP-9 On Acrolein-induced Mucus Hypersecretion

Objective: Mucus hypersecretion is a distinguishing pathophysiological feature of many airway diseases. MUC5AC is most important mucin that has been researched. The epidermal growth factor receptor (EGFR) is known to play a role in the regulation of cellular growth and differentiation. EGFR activation is probably involved in mucin expression in airway epithelium. Moreover, matrix metalloproteinase (MMPs), especially MMP-9, have been reported to promote the trasmigration of activated neutrophils. So increase the expreesion of EGFR. Here we will discuss the relationship between MMP-9 and mucus hypersecretion, in addition the possible mechanism of action.Methods: The rat airways mucus hypersecretion model was established by aerosol acrolein inhalation. Rats were exposed to acrolein alone (3.0 parts/million, 6h/day, together 12days), or doxycycline (20 mg/kg per day by gavage starting 2 days before and continuing throughout the acrolein period) or the group that only use doxycycline(20 mg/kg per day for 7 days). The expression of mucin was detected by AB-PAS staining and MUC5AC mRNA RT-PCR. The expression of MUC5AC mRNA and MMP-9 mRNA in trachea was detected by RT-PCR, and PCR products were photographed by agarose gel electrophoresis, and quantitated by densitometry. The proteins expression of MMP-9 was detected by immunohistochemical staining.Results: At 12 days of stimulation with acrolein ,the AB-PAS staining, the expression of MUC5AC mRNA and MMP-9 mRNA were obviously up-regulated in trachea in a time-dependent manner comparing with that in control group(P < 0.05). The AB-PAS staining, the expression of MUC5AC mRNA and MMP-9 mRNA were decreased after the treatment with doxycycline (P < 0.05 ). Immunocytochemical staining showed that positive MMP-9 staining was identified in acrolein-induced mucus hypersecretion rats, and decreased by treatment with doxycycline (P<0.05). The expression of MMP-9 mRNA was positively correlated with the expression of MUC5AC mRNA (F=66.753, PO.05).Conclusion: Aerosol acrolein inhalation increased AB-PAS staining and MUC5AC mRNA expression. It also induced MMP-9 expression in the trachea epithelium. And doxycycline—the MMPI, was found to significantly prevent MMP-9 expression; it also prevented MUC5AC mRNA expression. This study demonstrates that the MMP-9 is associated with acrolein-induced mucus hypersecretion.