Effect of the IkBα mutant gene delivery to mesenchymal stem cells on rat chronic pancreatitis

This study aimed to investigate the effect of inhibitors of the NF-kΒ alpha mutant gene (IkBaM) delivery to mensenchymal stem cells (MSCs) on rat chronic pancreatitis (CP). A total of 120 Sprague-Dawley rats were randomly divided into 6 groups of 20: Group A was injected with sterile saline solution...

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Bibliographic Details
Published in:Genetics and molecular research 2014-01, Vol.13 (1), p.371-385
Main Authors: Qin, T, Liu, C J, Zhang, H W, Pan, Y F, Tang, Q, Liu, J K, Wang, Y Z, Hu, M X, Xue, F
Format: Article
Language:English
Subjects:
Animals
Cytokines - genetics
Cytokines - metabolism
Dependovirus - genetics
Dependovirus - metabolism
Genetic Therapy
I-kappa B Proteins - genetics
I-kappa B Proteins - metabolism
Mesenchymal Stem Cell Transplantation
Mesenchymal Stromal Cells - metabolism
Mutation
NF-KappaB Inhibitor alpha
Pancreatitis, Chronic - therapy
Rats
Rats, Sprague-Dawley
Signal Transduction
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Summary:This study aimed to investigate the effect of inhibitors of the NF-kΒ alpha mutant gene (IkBaM) delivery to mensenchymal stem cells (MSCs) on rat chronic pancreatitis (CP). A total of 120 Sprague-Dawley rats were randomly divided into 6 groups of 20: Group A was injected with sterile saline solution, Group B was injected with allogenic MSCs, Group C1 was injected with allogenic IkBαM-MSCs cultured in vitro 4 h before CP modeling, Group C2 was injected with allogenic IkBαM-MSCs cultured in vitro during CP modeling, Group C3 was cultured with allogenic IkBαM-MSCs cultured in vitro 4 h after CP modeling, and Group D was injected with rAAV2-MSCs. Cytokine levels of ICAM-1, CTGF, IL-1, IL-6, IL-8, TNF-α, TIMP-1, TIMP-2, IL-10, FN, MMP-1, MMP-2, MMP-3, and MMP-9 were examined. The results indicated that allogenic IκBαM-MSCs could reduce pro-inflammatory cytokine levels and increase anti-inflammatory cytokine levels in CP. The allogenic IkBαM-MSCs reduced the activation and promoted the apoptosis of pancreatic stellate cells in the rat model of CP. IkBαM-MSCs influenced the proliferation and apoptosis of pancreatic stellate cells by regulating the activation of the PPAR, MAPK, mTOR, TGF-β, NOD-like receptor, Notch, WNT, TGF-β1-SMAD-2/3, and P53 signal transduction pathways.
ISSN:1676-5680
1676-5680
DOI:10.4238/2014.January.21.5