Bone marrow-derived mesenchymal stem cells attenuate acute liver injury and regulate the expression of fibrinogen-like-protein 1 and signal transducer and activator of transcription 3.

In recent years, bone marrow-derived mesenchymal stem cells (BMSCs) have been demonstrated to exert extensive therapeutic effects on acute liver injury; however, the underlying mechanisms of these effects have remained to be elucidated. The present study focused on the potential anti-apoptotic and pro-regenerative effects of BMSCs in D-galactosamine (D-Gal) and lipopolysaccharide (LPS)-induced acute liver injury in rats. An experimental rat acute liver injury model was established by intraperitoneal injection of D-Gal (400 mg/kg) and LPS (80 μg/kg). BMSCs and an identical volume of saline were administered via the caudal vein 2 h after the D-Gal and LPS challenge. Subsequently, the serum samples were collected to detect the levels of alanine aminotransferase and aspartate aminotransferase. Hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay and immunohistochemical staining were performed to determine apoptosis, regeneration and histological changes of liver sections. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect the protein and mRNA expression levels of fibrinogen-like-protein 1 (FGL1), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), STAT3 and B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) in liver tissue samples. The results indicated that intravenous transplantation of BMSCs significantly decreased the levels of alanine aminotransferase and aspartate aminotransferase, and reduced hepatocellular necrosis and inflammatory cell infiltration. Additionally, a terminal deoxynucleotidyl transferase-mediated nick-end labeling assay and immunohistochemical staining revealed that BMSC treatment reduced hepatocyte apoptosis and enhanced liver regeneration. Furthermore, Bcl-2 expression was increased, whilst the protein expression of Bax was reduced. The expression of FGL1 and p-STAT3 were elevated concurrently with the improvement of liver function. These results demonstrated that BMSCs may provide a promising potential agent for the prevention of acute liver injury via inhibition of hepatocyte apoptosis and acceleration of liver regeneration. The mechanism may be, a least in part, a consequence of the upregulation of FGL1 expression and the induction of STAT3 phosphorylation.