Effect of TGF-β1 on the Migration and Recruitment of Mesenchymal Stem Cells after Vascular Balloon Injury: Involvement of Matrix Metalloproteinase-14.

Abstract

Restenosis or occlusion after vascular procedures is ascribed to intimal hyperplasia. Transforming growth factor (TGF)-β1 is involved in recruitment of mesenchymal stem cells (MSCs) following arterial injury, and its release from latent TGF-binding protein by matrix metalloproteinase (MMP)-14-induced proteolysis contributes to neointima formation. However, the relationship between MMP-14 and TGF-β1 activation in restenosis is unknown. This study investigated the relationship using a rat model of balloon-induced injury. Rats were assigned to vehicle-, SB431542 (SB)-, or recombinant human (rh)TGF-β1-treated groups and examined at various time points after balloon-induced injury for expression of TGF-β1/Smad signalling pathway components, MMP-14 and MSCs markers including Nestin, CD29, and Sca1(+)CD29(+)CD11b/c(-)CD45(-). Intimal hyperplasia was reduced in SB- and rhTGF-β1-treated rats. The expression of TGF-β1, TGF-β1RI, and Smad2/3 was decreased, but the levels of phosphorylated Smad2/3 were higher in SB-treated rats than vehicle-treated after 7 days to 14 days. rhTGF-β1 administration decreased the expression of TGF-β1/Smad pathway proteins, except for TGF-β1RI. Nestin and CD29 expression and the number of Sca1(+)CD29(+)CD11b(-)CD45(-) cells were reduced, whereas MMP-14 expression was increased after SB431542 and rhTGF-β1 administration. These results suggest that TGF-β1/Smad signalling and MMP-14 act to recruit MSCs which differentiate to vascular smooth muscle cells and mesenchymal-like cells that participate in arterial repair/remodelling.

• Authors: Wei Zhao, Chengyan Wang, Ruixue Liu, Cuilei Wei, Juncang Duan, Kejian Liu, Shugang Li, Hong Zou, Jin Zhao, Lianghai Wang, Yan Qi, Weihua Liang, Jinfang Jiang, Wenjie Zhang, Lijuan Pang, Feng Li
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 21176 (Feb 16 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 26880204 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Smad Proteins
• Transforming Growth Factor beta1
• Matrix Metalloproteinase 14

Topics

• Animals
• Cell Movement
• Disease Models, Animal
• Endothelial Cells (metabolism)
• Humans
• Immunohistochemistry
• Matrix Metalloproteinase 14 (metabolism)
• Mesenchymal Stem Cells (drug effects, metabolism)
• Myocytes, Smooth Muscle (metabolism)
• Neointima (metabolism, pathology)
• Phenotype
• Rats
• Signal Transduction
• Smad Proteins (metabolism)
• Transforming Growth Factor beta1 (metabolism, pharmacology)
• Vascular Remodeling
• Vascular System Injuries (etiology, metabolism, pathology)