Expression of Smad7 and Smad ubiquitin regulatory factor 2 in a rat model of chronic pancreatitis

J Dig Dis. 2015 Jul;16(7):408-15. doi: 10.1111/1751-2980.12253.

Abstract

Objective: To quantify the expressions of Smad7 and Smad ubiquitin regulatory factor 2 (Smurf2) in the pancreas in rats with chronic pancreatitis (CP).

Methods: A total of 16 male Wistar rats were randomly divided into the control group and the CP group, with 8 rats in each group. CP was induced in vivo with dibutyltin dichloride (DBTC). Four weeks after DBTC administration, histological assessment and the measurement of hydroxyproline content in the pancreatic tissues were performed to assess the inflammation and fibrosis of the pancreas. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) for transforming growth factor (TGF)-β1 and α-smooth muscle actin (α-SMA) were applied to assess activated pancreatic stellate cells (PSC) and TGF-β1 expression. Smad7 and Smurf2 expressions in the pancreas were measured using Western blot and RT-PCR.

Results: Typical histopathological characteristics of DBTC-induced CP in the rats with extensively activated PSC. Compared with the control group, the expressions of TGF-β1, α-SMA and hydroxyproline content in the pancreatic tissues in the CP group were significantly increased. Meanwhile, the mRNA and protein expressions of Smad7 and Smurf2 were significant increased in the fibrotic pancreas, in which the expressions of Smad7 proteins showed an obvious reduction compared with controls.

Conclusion: The dysregulation of Smad7 and Smurf2 may be associated with the pathogenesis of pancreatic fibrosis through the TGF-β signaling pathway.

Keywords: Smad ubiquitin regulatory factor 2; Smad7; chronic pancreatitis; expression; pancreatic fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Blotting, Western
  • Hydroxyproline / analysis
  • Male
  • Organotin Compounds
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatic Stellate Cells / metabolism
  • Pancreatitis, Chronic / chemically induced
  • Pancreatitis, Chronic / genetics
  • Pancreatitis, Chronic / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Smad7 Protein / metabolism*
  • Transforming Growth Factor beta1 / metabolism
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Acta2 protein, rat
  • Actins
  • Organotin Compounds
  • RNA, Messenger
  • Smad7 Protein
  • Smad7 protein, rat
  • Transforming Growth Factor beta1
  • Smurf2 protein, rat
  • Ubiquitin-Protein Ligases
  • dibutyldichlorotin
  • Hydroxyproline