Figure 3. Mechanisms of PaSC activation.

Exposure of the pancreas to ethanol, to its metabolites, and to insults that generate ROS all result in PaSC activation by autocrine and paracrine products. The paracrine factors are derived from neighboring cells such as acinar cells, ductal cells, endothelial cells, and leukocytes. Activated PaSCs can migrate to sites of tissue damage, undergo regulated contraction, proliferate, phagocytose, and generate products that modulate the ECM by facilitating repair or promoting fibrosis (17, 42, 56, 69). Persistent activation of PaSCs promotes fibrosis, while redifferentiation to a quiescent state or stimulation to undergo apoptosis facilitates tissue repair.