RESUMO
Stem cells and gene therapy have become promising strategies for treating ischemic diseases and regenerating tissue. Hepatocyte growth factor (HGF) is an angiogenic growth factor with multiple functions, including promoting angiogenesis, regulating inflammation, inhibiting fibrosis, and activating tissue regeneration. Numerous preclinical experiments and clinical trials have demonstrated the feasibility and efficacy of HGF gene therapy in the treatment of ischemic diseases and tissue regeneration. This review summarizes the current advances of therapeutic angiogenesis using HGF gene transfer and modified stem cells. The physiological roles of HGF in angiogenesis and tissue regeneration are revisited. The current advances of clinical trials of plasmid and adenovirus HGF in the treatment of critical limb ischemia and coronary heart disease in China are introduced. Furthermore, valuable insight is provided into the prospective future of novel regenerative strategies using HGF-modified mesenchymal stem cells. HGF gene therapy is presented as a promising therapeutic approach in the treatment of ischemic diseases and regenerative medicine.
Assuntos
Doença das Coronárias/terapia , Terapia Genética/tendências , Fator de Crescimento de Hepatócito/uso terapêutico , Isquemia/terapia , China , Doença das Coronárias/genética , Fator de Crescimento de Hepatócito/genética , Humanos , Isquemia/genética , Regeneração/genética , Medicina Regenerativa/tendênciasRESUMO
OBJECTIVE: To investigate the effect and mechanism of miR-486 on glycometabolism of hematopoietic cells. METHODS: qRT-PCR was applied to detect the expression of miR-486 or Sirt1 on TF-1 cells under hypoxia. Lentivirus was used to mediate the overexpression or inhibition of miR-486 on TF-1 cells and qRT-PCR was used to detect the expressions of Sirt1, glucose transporter 1(Glut1) and glucose transporter 4(Glut4). Lentivirus-mediated Sirt1-shRNA transduction was used to knockdown Sirt1 expression which was detected by qRT-PCR and Western blot. The expressions of Glut1 and Glut4 were determined by qRT-PCR. RESULTS: Hypoxia promoted the expression of miR-486 and inhibited the expression of Sirt1. MiR-486 overexpression could inhibit the expression of Sirt1 and promote the expressions of Glut1 and Glut4, whereas miR-486 silencing upregulated the sirt1 expression and inhibited the expressions of Glut1 and Glut4. And inhibition of Sirt1 expression increased the expressions of Glut1 and Glut4. CONCLUSION: MiR-486 can regulate the glycometabolism of hematopoietic cells by targeting Sirt1.
Assuntos
Células-Tronco Hematopoéticas/fisiologia , MicroRNAs/fisiologia , RNA Interferente Pequeno , Sirtuína 1/fisiologia , Técnicas de Silenciamento de Genes , Humanos , LentivirusRESUMO
MicroRNAs (miRNAs) regulate the hypoxia-induced erythroid differentiation of hematopoietic cells. In this study, we identified that miR-486 was a rapid response miRNA to hypoxia in erythroleukemia TF-1 cells. Hypoxia exposure increased both intracellular and miR-486 levels of TF-1 cells. Ectopic miR-486 expression enhanced the growth and erythroid differentiation of TF-1 cells, whereas miR-486 inhibition suppressed their growth and erythroid differentiation. Treatment of TF-1 and cord blood CD34+ cells with exogenous containing miR-486 resulted in an increase of intracellular miR-486 level and enhanced erythroid differentiation. Furthermore, we identified that Sirt1 is a miR-486 target gene which modulates hypoxia-induced erythroid differentiation of TF-1 cells. Thus we identified a novel miRNA regulatory network that contributes to hypoxia-induced erythroid differentiation of hematopoietic cells.
