Delayed response toward activation stimuli in pancreatic stellate cells

Pancreatic stellate cells (PSCs) are known to be crucially involved in the development of pancreatic fibrosis, a characteristic feature of chronic pancreatitis and pancreatic cancer. The key event in the pathogenesis of fibrosis represents a transition process of quiescent PSCs into a myofibroblastlike phenotype associated with cell activation in terms of proliferation and synthesis of profibrogenic substances. There is little information available regarding the dynamics of the complex processes initiated by an activating stimulus in quiescent stellate cells.

Using microarray analysis, we characterized the expression profiles during PSC activation caused by in vitro cultivation on days 2, 4, 7, and 14 after cell isolation. Activation status has been identified by the expression of the activation marker alpha-smooth muscle actin. Genes of interest were subjected to reverse transcription-polymerase chain reaction. To test biologic functions, the responsiveness of stellate cells toward the activators activin A and transforming growth factor-beta1 was investigated in dependence on the cell transition status.

Our results revealed that freshly isolated (=quiescent) PSCs were refractory to stimuli for several days, a phenomenon that we referred to as delay phase.

The retarded response could be considered a protection mechanism to prevent inappropriate stellate cell activation.