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Am J Transl Res. 2017 Mar 15;9(3):1500-1508. eCollection 2017.

Expression of antisense of microRNA-26a-5p in mesenchymal stem cells increases their therapeutic effects against cirrhosis.

Author information

1
Department of Emergency, Chinese PLA General Hospital 28 Fuxing Road, Beijing 100853, China.
2
Department of Emergency, Liuzhou General Hospital 8 Wenchang Road, Liuzhou 545005, China.
3
Department of General Thoracic Surgery, Chinese PLA General Hospital 28 Fuxing Road, Beijing 100853, China.
4
Department of Orthopaedics, Chinese PLA General Hospital 28 Fuxing Road, Beijing 100853, China.
5
Department of Geriatric Cardiovascular, Chinese PLA General Hospital 28 Fuxing Road, Beijing 100853, China.
6
Department of Oncology Surgery, Chinese PLA General Hospital 28 Fuxing Road, Beijing 100853, China.
7
Department of Ultrasound, Chinese PLA General Hospital 28 Fuxing Road, Beijing 100853, China.

Abstract

Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes, and has been shown to prevent cirrhosis during liver regeneration. Transplantation of mesenchymal stem cells (MSCs) reduces the development of cirrhosis after liver injury. However, the production and secretion of transplanted MSCs in liver were not studied yet. Here we found that the MSCs expressed low levels of HGF protein, but surprisingly high levels of HGF mRNA. Further investigation using bioinformatics analyses and luciferase reporter assay showed that MSCs expressed high levels of microRNA-26a-5p (miR-26a-5p), which targeted 3'-UTR of HGF mRNA to inhibit its protein translation. In vivo, miR-26a-5p-depleted MSCs were transplanted into mice with carbon tetrachloride (CCl4)-induced cirrhosis. We found that suppression of miR-26a-5p in MSCs further ameliorated the severity of liver fibrosis, reduced the portal hypertension and sodium retention, compared to transplantation of control MSCs. Hence, our study suggests that suppression of miR-26a-5p in MSCs may improve their therapeutic effects against cirrhosis through increasing HGF production.

KEYWORDS:

Mesenchymal stem cells (MSCs); cirrhosis; hepatocyte growth factor (HGF); miR-26a-5p

PMID:
28386375
PMCID:
PMC5376040

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