Effects of FGF21-secreting adipose-derived stem cells in thioacetamide-induced hepatic fibrosis.
Hwansu KangEunhui SeoJong-Moon ParkNa-Young HanHookeun LeeYoon Sin OhPublished in: Journal of cellular and molecular medicine (2018)
Mesenchymal stem cells (MSCs) have been investigated to treat liver diseases, but the efficiency of MSCs to treat chronic liver diseases is conflicting. FGF21 can reduce inflammation and fibrosis. We established FGF21-secreting adipose derived stem cells (FGF21_ADSCs) to enhance the effects of ADSCs and transplanted them into thioacetamide (TAA)-induced liver fibrosis mice via the tail vein. Transplantation of FGF21_ADSCs significantly improved liver fibrosis by decreasing serum hyaluronic acid and reducing the expression of fibrosis-related factors such as α-smooth muscle actin (α-SMA), collagen and tissue inhibitor of metalloproteinase-1 (TIMP-1) compared with the Empty_ADSCs by inhibition of p-JNK, NF-κB and p-Smad2/3 signalling. α-lactoalbumin (LA) and lactotransferrin (LTF), secretory factors produced from FGF21_ADSCs inhibited TGF-β1-induced expression of α-SMA and collagen in LX-2 cells. These results suggest that transplantation of FGF21_ADSCs inhibited liver fibrosis more effectively than Empty_ADSCs, possibly via secretion of α-LA and LTF.
Keyphrases
- liver fibrosis
- mesenchymal stem cells
- high glucose
- smooth muscle
- diabetic rats
- hyaluronic acid
- poor prognosis
- oxidative stress
- induced apoptosis
- signaling pathway
- drug induced
- transforming growth factor
- wound healing
- epithelial mesenchymal transition
- type diabetes
- long non coding rna
- cell death
- high fat diet induced
- cell cycle arrest
- pi k akt
- insulin resistance