Portal hypertensive gastric mucosa has reduced activation of MAP kinase (ERK2) in response to alcohol injury: a key to impaired healing?

Portal hypertensive (PHT) gastric mucosa has increased susceptibility to injury and impaired mucosal healing. Because our previous study showed that ulcer-induced activation of mitogen-activated protein (MAP) kinase (ERK) plays a pivotal role in gastric mucosal healing, we investigated whether ERK activation is altered in PHT gastric mucosa following alcohol injury. We studied ERK2 phosphorylation and activity and expression of MAP kinase phosphatase-1 (MKP-1) in gastric mucosa of PHT and sham-operated (SO) normal rats both at baseline and following alcohol injury. In SO gastric mucosa, ERK2 phosphorylation and activity were significantly increased time-dependently following alcohol injury: by 221% and 137%, respectively at 24 h vs. baseline. In contrast, in PHT gastric mucosa following alcohol injury, neither ERK2 phosphorylation nor activity was increased versus baseline. In PHT gastric mucosa, MKP-1 mRNA and protein expression were increased at baseline versus SO rats and were increased further following alcohol injury with values higher by 20%-40% at each study time versus SO rats. Because ERK2 is crucial for mucosal healing, reduced ERK2 activation resulting from the overexpression of MKP-1 might be the basis for the impaired mucosal healing in PHT gastric mucosa.