Change of p16(INK4a) and PCNA protein expression in myocardium after injection of hIGF-1 gene modified skeletal myoblasts into post-infarction rats
| Autor: | Guanhua Su, Yong-xin Lu, Shu-ling Rong, Yan-zhang Gao, Shao-hua Mi, Xiaoming Liu |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Genetic enhancement Myoblasts Skeletal Biomedical Engineering Myocardial Infarction Hindlimb Biochemistry Protein expression Biomaterials Rats Sprague-Dawley Internal medicine Proliferating Cell Nuclear Antigen Genetics medicine Myocyte Animals Insulin-Like Growth Factor I Gene Cyclin-Dependent Kinase Inhibitor p16 Earth-Surface Processes biology Myocardium Genetic Therapy medicine.disease Molecular biology Proliferating cell nuclear antigen Rats Endocrinology Heart failure PncA biology.protein |
| Zdroj: | Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban. 28(4) |
| ISSN: | 1672-0733 |
| Popis: | This study examined the change of p16(INK4a) and PCNA protein expression in myocardium after injection of hIGF-1 gene modified skeletal myoblasts into post-infarction rats. HIGF-1 gene modified skeletal myoblasts (hIGF-1-myoblasts) were injected into hind limb muscles of 18 post-infraction rats (experimental group). Primary-myoblasts were injected into 18 post-infraction rats (control group) and 12 non-infarction rats (sham group). Expression of p16(INK4a) and PCNA protein in myocardiums were separately detected immunocytochemically 1, 2 and 4 weeks after the injection. The level of hIGF-1 and rIGF-1 protein in serum and myocardium were detected by enzyme-linked immunosorbent assay (ELISA). Compared with the sham group, the percentage of p16(INK4a) and PCNA positive cells reached a peak after 1 week in the control group and the experimental group (P0.01). Moreover, the percentage of p16(INK4a)-positive cells in the experimental group was lower than in control group whereas the percentage of PCNA-positive cells was lower in the control group than in the experimental group (P0.01). The percentage of p16(INK4a)-positive cells in the experimental group and the percentage of PCNA-positive cells in the control group were close to that in the sham group from the 2nd week (P0.05). ELISA analysis disclosed that the myocardium level of rIGF-1 protein increased gradually in the controls and especially in the experimental group (P0.01). The serum level of rIGF-1 decreased significantly in post-infraction rats, but these conditions were improved in the experimental group (P0.01). The hIGF-1 protein in serum and myocardium were detected from the 1st week to the 4th week in the experimental group. Statistical analysis revealed significant associations of myocardium level of hIGF-1 protein with expression of p16(INK4a) and PCNA protein (r=-0.323, P0.05; r=0.647, P0.01). It is concluded that genetically hIGF-1-myoblast provides a means for constant synthesis and release of hIGF-1. It could not only improve the expression of rIGF-1 and PCNA protein in myocardium, but also suppress the expression of p16(INK4a) protein for 30 days in post-infraction rats. Myoblasts-mediated IGF-1 gene therapy may provide a new alternative for the clinical treatment of heart failure. |
| Databáze: | OpenAIRE |
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