The role of chemokines in proangiogenic action induced by human adipose tissue-derived mesenchymal stem cells in the murine model of hindlimb ischemia.
The proangiogenic action of human adipose tissue-derived mesenchymal stem cells (hASCs) transplantation has been shown to be mediated by secretory factors. In this study, we determined if human granulocyte chemotactic protein-2(GCP2) or monocyte chemoattractant protein-1(MCP1) is involved in the proangiogenic action of hASCs transplantation in the hindlimb ischemia model. hASCs secrete GCP2 and MCP1, which leads to increased tubule formation. The downregulation of GCP2 or MCP1 decreased MCP1 and GCP2 secretion, respectively, whereas the external addition of GCP2 or MCP1 increased MCP1 and GCP2, respectively. Additionally, the treatment of GCP2 and MCP1 increased VEGF secretion, while the downregulation of GCP2 and MCP1 showed the opposite effect on VEGF secretion. Downregulation of GCP2 and MCP1 expression also inhibited hASCs-induced proangiogenic action, while the overexpression of GCP2 increased it. Finally, the downregulation of MCP1 or VEGF inhibited the GCP2 overexpression-induced increase in blood flow recovery. Taken together, these data indicate that the proangiogenic action of hASCs transplantation is mediated by the interaction between GCP2, MCP1 and VEGF, which are secreted from the transplanted cells.
Cho
Hyun Hwa
HH
Department of Physiology, Pusan National University, Yangsan, Korea.
Kim
Yeon Jeong
YJ
Kim
Jong Tae
JT
Song
Ji Sun
JS
Shin
Keun Koo
KK
Bae
Yong Chan
YC
Jung
Jin Sup
JS
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054427:Chemokine CXCL6 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006614:Hindlimb; D006801:Humans; D007511:Ischemia / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D034741:RNA, Small Interfering / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D018932:Chemokine CCL2; D054427:Chemokine CXCL6; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A