Effect of TGF-β1 on the Migration and Recruitment of Mesenchymal Stem Cells After Vascular Balloon Injury: Involvement of Matrix Metalloproteinase-14
Authors
Affiliations
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.
Nguyen H, Vuong C, Fukushige M, Usuda M, Takagi L, Yamashita T Front Oncol. 2024; 14:1346312.
PMID: 38515582 PMC: 10955079. DOI: 10.3389/fonc.2024.1346312.
Impact of the transforming growth factor-β pathway on vascular restenosis and its mechanism.
Luo Z, Li X, Wang L, Shu C Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023; 48(8):1252-1259.
PMID: 37875366 PMC: 10930841. DOI: 10.11817/j.issn.1672-7347.2023.230064.
Yu S, Yu S, Liu H, Liao N, Liu X Stem Cell Res Ther. 2023; 14(1):235.
PMID: 37667383 PMC: 10478247. DOI: 10.1186/s13287-023-03476-4.
Pathogenesis of pulmonary hypertension caused by left heart disease.
Xiao M, Lai D, Yu Y, Wu Q, Zhang C Front Cardiovasc Med. 2023; 10:1079142.
PMID: 36937903 PMC: 10020203. DOI: 10.3389/fcvm.2023.1079142.
Macrophage TGF-β signaling is critical for wound healing with heterotopic ossification after trauma.
Patel N, Nunez J, Sorkin M, Marini S, Pagani C, Strong A JCI Insight. 2022; 7(20).
PMID: 36099022 PMC: 9714796. DOI: 10.1172/jci.insight.144925.