Effects of oxidative stress on the activation of pancreatic stellate cells through the up-regulation of fibromodulin

Objective To investigate the role of fibromodulin (FMOD) in the xidative stress induced activation of pancreatic stellate cells (PSCs). Methods Lentivirus containing ShRNA targeting FMOD (sh-FMOD) was transfected into PSCs, and then the prooxidant menadione (MND) was used to treat PSCs for 24 h (MND+ sh-FMOD group). Lentivirus transfected PSCs cells treated by a equal volume of DMSO served as sh-FMOD group, parent cells as control group and PSCs treated by MND as MND group. RT-PCR were used to detect the mRNA expression of the markers of activated PSCs including α-SMA, Col3α1, Col1α1, TIMP1 and α1-integrin. Chronic pancreatitis (CP) rat model was induced by DBTC infusion into the tail vein. Immunohistochemical (IHC) staining was used to detect the protein expression of FMOD, FN, α-SMA, SOD and MDA in normal pancreatic tissue and CP tissue. Results FMOD mRNA expression of the PSCs in FMOD group was obviously lowerer than that in control group (0.16±0.03 vs 1), and the difference was statistically significant (P<0.01), indicating that FMOD was successfully silenced. The mRNA expression of FMOD, α-SMA, Col3α1, Col1α1, TIMP1 and α1-Integrin of PSCs in MND group was obviously higher than those in control group, which in MND+ sh-FMOD group was lower than those in MND group, and the difference was statistically significant (P<0.05 or <0.01). Compared with those in normal pancreatic tissue, the protein expression of FMOD, α-SMA, SOD and MDA in CP tissue was up-regulated, and the difference was statistically significant (all P<0.05). Conclusions Oxidative stress can facilitate the activation of PSCs through the induction of fibromodulin expression. Key words: Pancreatitis, chronic; Pancreatic stellate cells; Oxidative stress; Fibromodulin