Src Homology 2-containing Protein Tyrosine Phosphatase-2 Acts As a Negative Regulator for MUC5AC Transcription Via the Inhibition of the ERK1/2 MAPK Signalling Pathway in the Airway

Aims: Mucus hypersecretion has been frequently observed in inflammation respiratory diseases. However, the negative regulators for mucus overproduction have not been readily identified. Our work focused on identifying novel negative regulator that modulates mucus overproduction in the human respiratory system. Herein, we examined whether H2 O2 could induce MUC5AC transcription in a dose-dependent manner and activate tyrosine phosphatase (SHP)-2 in human airway epithelial cells.

Methods: We performed qRT-PCR to detect the changes in MUC5AC transcription and dot-blotting analysis to investigate MUC5AC secretion as regulated by SHP-2.

Results: H2 O2 induced MUC5AC transcription in a dose-dependent manner and dramatically activated SHP-2. In addition, whereas wild-type SHP-2 completely inhibited H2 O2 -induced MUC5AC transcription, siRNA-SHP-2 restored it interestingly, suggesting that SHP-2 may act as a negative regulator for mucus overproduction and hypersecretion in the human respiratory tract. Moreover, SHP-2 inhibited the ERK1/2 MAPK pathway, thus abolishing the signalling for MUC5AC transcription.

Conclusion: We found that H2 O2 induced SHP-2 activation, which acted as a suppressor in H2 O2 signalling to regulate MUC5AC transcription in the airway.