EPA and DHA Differentially Inhibit Epithelial-to-Mesenchymal Transition and Decrease Collagen Deposition in Intestinal Fibrosis
Intestinal fibrosis is a serious complication of inflammatory bowel disease(IBD),however,no effective pharmacological treatment for intestinal fibrosis has been found yet.ω-3 PUFAs have re-ceived extensive attention for their anti-fibrotic effects in other organs,but their roles and mechanism in curing intestinal fibrosis are still unclear.In the present study,we compared the anti-fibrotic effects of EPA,DHA and fish oil in intestinal fibrosis mice using a TNBS(2,4,6-trinitrobenzene sulfonic acid)-induced intestinal fibrosis mouse model.Forty 8-week-old male BALB/C mice were randomly divided into five groups.Compared with the DHA and fish oil groups,EPA intervention more effectively alleviated weight loss,reduced colon length shortening,lowered disease activity index scores,and significantly im-proved inflammatory responses in the mice(P＜0.05).EPA inhibited the expression of pro-inflammatory cytokines TNF-α,IL-6,and IL-17,and promoted the expression of anti-inflammatory cytokine IL-10.EPA intervention significantly reduced the colonic histological severity of fibrosis,decreased col1a2,col3a2 and hydroxyproline expression in the colon,and EPA levels in the colon were negatively correlated with intestinal fibrosis scores(R2=0.7383,P＜0.0004;R2=0.4608,P＜0.0152).EPA up-regulated the expression of p-AMPK,ULK1,LC3 and p62,and also inhibited mTOR expression and the epithelial-to-mesenchymal transition(EMT)in intestinal epithelial cells.EPA inhibited α-SMA,TGF-β1,vimen-tin,TIMP-1(tissue inhibitors of metalloproteinases-1,TIMP-1)expression,and increased MMP-9(ma-trix metalloproteinase-9,MMP-9)expression,which inhibited activation of intestinal mesenchymal cells and alleviated excessive deposition of extracellular matrix(ECM).EPA restored Th17/Treg balance,maintained intestinal immune homeostasis,inhibited EMT in intestinal epithelial cells,regulated TIMPs/MMPs balance,and effectively alleviated the excessive deposition of colonic ECM in intestinal fibrosis mice.EPA is expected to be a novel adjuvant therapy for food-borne IBD with anti-fibrosis,and suggests that the autophagy pathway may play a role in inhibiting EMT.
NETL
NSTL
万方数据
维普
