MicroRNA differential expression in liver cirrhosis rats undergoing human umbilical cord mesenchymal stem cell transplantation / 中国组织工程研究

ABSTRACT

BACKGROUND:Human umbilical cord mesenchymal stem cels (hUC-MSCs) can obviously relieve liver cirrhosis, and thereby repair liver injury. However, the molecular mechanism of hUC-MSCs therapy for liver cirrhosis is limited at present, and especialy the non-coding RNA regulation of hepatic gene changes has not been detailed. OBJECTIVE:To investigate the changes of microRNA after hUC-MSCs therapy in rats with liver cirrhosis. METHODS:Liver cirrhosis models were established in rats using carbon tetrachloride subcutaneous injection plus oral administration of alcohol. At 8 weeks after modeling, hUC-MSCs were injectedvia the tail vein once a week for 4 consecutive weeks. At 1 week after the last injection, rat liver tissues were colected for paraffin embedding. Liver RNA was extracted for gene chip analysis. Blood samples were colected and analyzed using an automatic biochemical analyzer to detect the changes of liver function. RESULTS AND CONCLUSION:Alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transpeptidase were improved significantly after hUC-MSCs therapy. Fat lesions and necrosis of hepatocytes were significantly reduced. MicroRNA expression microarray hybridization analysis and PCR results showed that rno-miR-369-5p, rno-miR-3584-5p and rno-miR-153* were down-regulated during modeling and increased after hUC-MSCs therapy. And rno-miR-93, rno-miR-199a-3p, rno-miR-195, rno-let-7a and rno-miR-19a were firstly up-regulated in the process of modeling and then down-regulated obviously after hUC-MSCs therapy. These results suggest that hUC-MSCs may reverse liver cirrhosis and liver cel damage through up-regulation of rno-miR-369-5p, rno-miR-3584-5p and rno-miR-153*, and down-regulation of rno-miR-93, rno-miR-199a-3p, rno-miR-195, rno-let-7a and rno-miR-19a.