Figure 6-6940.

MMPs mediate stretch-induced ERK1/2 activation. A: ERK1/2 activation is seen in response to stretch injury and is blocked by addition of doxycycline. Bladders (n = 3) were stretched 15 minutes ex vivo after a 1-hour incubation in doxycycline (doxy) or vehicle control (EtOH). B: Similarly, GM6001 treatment decreases ERK1/2 activation in response to stretch injury. Bladders (n = 3) were stretched for 15 minutes ex vivo after a 1-hour incubation in increasing concentrations of GM6001 or vehicle control (NS, 0). C: Conditioned medium from distended bladders also induced MMP-dependent ERK1/2 phosphorylation in BSMCs. MMP inhibition by doxycycline prevented ERK1/2 activation in BSMC response to distension-conditioned medium. Bladders (n = 3) were distended ex vivo in the presence of doxycycline or were undistended. Conditioned medium was added in vitro to BSMCs for 5 minutes, and BSMC protein was analyzed by Western blotting.