Mobilization of Bone Marrow Mesenchymal Stem Cells Inhibits TGF-β Non-classical Pathway Against Myocardial Fibrosis in Rats

XIA Wen-qing, YUAN Xiang-zhen, LU Huai-zhi, LIU Yang, DU Da-yong , LI Yun-tian

Abstract

To observe the relationship between the mechanism of bone marrow stem cell mobilization mediated the myocardial fibrosis inhibition in rats and the non-classical pathway mediated by transforming growth factor-β (TGF-β).  Methods  Twenty two Wistar rats were subcutaneously injected with isoproterenol (Iso) to establish the model of myocardial fibrosis, and then were randomly divided into control group and granulocyte colony-stimulating factor (G-CSF)-treat group (GT group). The rats in GT group were subcutaneously injected with recombinant human granulocyte stimulating factor for 5 days, and the control group was injected with normal saline. After 4 weeks, the myocardial structure was observed by pathological staining, the content of serum B type natriuretic peptide (BNP) was detected by ELISA , the expression of type Ⅲ collagen was detected by immunohistochemistry staining and the protein expression level of typeⅠcollagen, TGF-β, transforming growth factor kinase 1 (TAK1), mitogen-activated protein kinase kinase (MKK) and p38 mitogen-activated protein kinase (p38MAPK) was determined by Western blot.  Results  Compared with the control group, the serum BNP level, Masson staining collagen deposition, collagen area ratio and the expression of typeⅠcollagen, TGF- β, TAK1, MKK3 and p38MAPK in the GT group were lower than those in the control group.  Conclusion  Bone marrow stem cell mobilization can alleviate the degree of myocardial fibrosis in rats, which is related to the inhibition of TGF- β/TAK1/MKK/p38MAPK pathway.

 

Keywords: Isoproterenol, Granulocyte colony-stimulating factor, Cardiac fibrosis, TGF-β

 

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