Effects of Hydrogen Sulfide on Rat Pancreatic Stellate Cells

Objectives: Pancreatic stellate cells (PSCs) play a crucial role during pancreatic fibrosis development. Hydrogen sulfide (H(2)S) is a recently discovered gaseous transmitter, whose role in PSCs has not been explored yet. In the present study, we examined the effects of sodium hydrosulfide (NaHS), an H(2)S donor, on rat PSCs and elucidated the mechanisms involved. Methods: Primary PSCs were isolated from rat pancreatic tissue. Lactate dehydrogenase and caspase assays were performed to detect cell death. Pancreatic stellate cell proliferation was determined by cell count analyses, bromodeoxyuridine incorporation, and flow cytometry. The role of heme oxygenase-1 (HO-1) was assessed by pharmacological HO inhibition and transfection of HO-1 small interfering RNA. Pancreatic stellate cell migration was determined by a wound healing assay, and PSC contraction was assessed by a gel contraction assay. alpha-Smooth muscle actin, collagen type I, and fibronectin messenger RNAs were analyzed by real-time polymerase chain reaction. Results: NaHS inhibited PSC proliferation at nontoxic concentrations. This was associated with HO-1-mediated repression of extracellular signal-regulated kinase 1/2 signaling. NaHS suppressed PSC migration and activation as well as extracellular matrix synthesis. Conclusions: The results of the present study indicate that NaHS inhibits key cell functions of PSCs. Administration of H(2)S-releasing compounds might represent a novel strategy in the treatment of pancreatic fibrosis.