Effect of TGF-?1 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)-?1 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-?1 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-?1-treated groups and examined at various time points after balloon-induced injury for expression of TGF-?1/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-?1-treated rats. The expression of TGF-?1, TGF-?1RI, 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-?1 administration decreased the expression of TGF-?1/Smad pathway proteins, except for TGF-?1RI. 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-?1 administration. These results suggest that TGF-?1/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.

SUBMITTER: Zhao W 

PROVIDER: S-EPMC4754777 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature