title: Effects of hydrogen sulfide on rat pancreatic stellate cells.
abstract: OBJECTIVE
  Pancreatic stellate cells (PSCs) play a crucial role during pancreatic fibrosis development. Hydrogen sulfide (H2S) 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 H2S 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. α-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.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Christian I
authors.initials: CI
authors.lastname: Schwer
authors.forename: Patrick
authors.initials: P
authors.lastname: Stoll
authors.forename: Ulrich
authors.initials: U
authors.lastname: Goebel
authors.forename: Hartmut
authors.initials: H
authors.lastname: Buerkle
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoetzel
authors.forename: Rene
authors.initials: R
authors.lastname: Schmidt
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D058954:Pancreatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000199:Actins; D024042:Collagen Type I; D005353:Fibronectins; D013440:Sulfides; D051547:Heme Oxygenase-1; D020928:Mitogen-Activated Protein Kinases; C025451:sodium bisulfide; D006862:Hydrogen Sulfide