Mesenchymal Stem Cells SuppressTGF-β Release to Decrease α-SMAExpression in Ameliorating CCl4-Induced Liver Fibrosis

ABSTRACT
Introduction: Liver fibrosis (LF) is the excessive deposition of extracellular matrix (ECM),
produced by overactivated hepatic stellate cells, following prolonged transforming growth
factor-β (TGF-β) stimulation. The ability of mesenchymal stem cells (MSCs) to improve LF
has been reported. However, the mechanisms of MSCs to ameliorate LF through suppressing
TGF-β and α-smooth muscle actin (α-SMA) remains unclear. Aim: To investigate the effects
of MSCs treatment on suppressing TGF-β levels and decreasing α-SMA expression in
an LF model. Methods: In this study, wenty-four male Wistar rats were injected intraperitoneal
(IP) with carbon tetrachloride (CCL4), twice weekly, for eight weeks, to induce LF. Rats
were randomly assigned to six groups: Sham, Control, Sham-lo, Sham-hi, and MSC-treated
groups, at doses of 1 x 106 (T1) and 2×106 (T2) cells. TGF-β levels were analyzed by enzyme-
linked immunosorbent assay (ELISA), whereas α-SMA expression was determined
by immunohistochemistry staining. Results: MSCs decreased the expression of TGF-β in
T1 and T2 groups on day 3 and 14. The T2 group showed lower TGF-β levels than that in the
T1 group. This finding was in line with the observed decrease in α-SMA expression and the
number of collagen. Conclusion: MSCs treatment ameliorated LF by suppressing TGF-β
production, leading to decreased α-SMA expression in a CCL4-induced LF animal model.
Keywords: Liver Fibrosis, Mesenchymal Stem Cells, transforming growth factor-beta, alpha-smooth
muscle actin.

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