Novel insights into a treatment for aplastic anemia based on the advanced proliferation of bone marrow-derived mesenchymal stem cells induced by fibroblast growth factor 1

摘要

Aplastic anemia (AA) is rare disease that is predominantly observed in adolescents. Without effective management at an early stage, is associated with a high risk of mortality. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into various types of cell, which are able to produce a number of hematopoietic growth factors considered to be important in AA alleviation. However, the mechanism underlying the role of fibroblast growth factor 1 (FGF1) in BMSC differentiation remains unknown. In the current study, the investigation focused on the regulatory role and potential signaling pathway of FGF1 in BMSC differentiation in patients exhibiting AA. BMSCs were infected with Ad-FGF1 and presented a potent proliferation capability, which was evaluated using Cell Counting kit-8 analysis. Reverse transcription-quantitative polymerase chain reaction revealed that long non-coding (lnc)RNA of testis development related gene 1 (TDRG1) was significantly upregulated, demonstrating high expression at the transcriptional level in the BMSCs that were infected with Ad-FGF1. The decreased proliferation capability of BMSCs that were treated with Ad-FGF1 and TDRG1-small interfering RNA validated the vital effect of TDRG1 on the FGF1 regulatory process of BMSC differentiation. Further experiments revealed that the increase of acetyl-histones, H3 and H4 was diminished in the TDRG1 promoter of BMSCs that were infected with Ad-FGF1, which indicated that the process of acetylation was promoted when the BMSCs were infected with Ad-FGF1. Thus, it was inferred that FGF1 induces the proliferation of BMSCs in patients with AA via promoting acetylation in lncRNA of the TDRG1 gene promoter.