title: Basic Fibroblast Growth Factor Induces Angiogenic Properties of Fibrocytes to Stimulate Vascular Formation during Wound Healing.
abstract: The role of fibrocytes in wound angiogenesis remains unclear. We therefore demonstrated the specific changes in fibrocyte accumulation for angiogesis in basic fibroblast growth factor (bFGF)-treated wounds. bFGF-treated wounds exhibited marked formation of arterioles and inhibition of podoplanin+lymph vessels that were lacking in vascular endothelial growth factor-A-treated wounds. Real-time PCR in bFGF-treated wounds manifested enhanced expression of CD34, CD31, and bFGF mRNA and reduced expression of podoplanin and collagen type I, III, and IV mRNA. Double immunofluorescence staining focusing on fibrocyte detection in bFGF-treated wounds showed increased formation of capillary-like structures composed of CD34+/procollagen I+fibrocytes, with a lack of capillary-like structures formed by CD45+/procollagen I+or CD11b+/procollagen I+fibrocytes. However, vascular endothelial growth factor-A-treated wounds lacked capillary-like structures composed of CD34+/procollagen I+fibrocytes, with increased numbers of CD34+/fetal liver kinase-1+endothelial progenitor cells. Furthermore, fibroblast growth factor receptor 1 siRNA injection into wounds, followed by bFGF, inhibited the formation of capillary-like structures composed of CD34+/procollagen I+fibrocytes, together with inhibited mRNA expression of CD34 and CD31 and enhanced mRNA expression of collagen type I, indicating the requirements of bFGF/fibroblast growth factor receptor 1 system for capillary structure formation. This study highlights the angiogenic properties of CD34+/procollagen I+fibrocytes specifically induced by bFGF, providing new insight into the active contribution of fibrocytes for vascular formation during wound healing.
authors: Department of Plastic and Reconstructive Surgery, Toho University Omori Medical Center, Tokyo, Japan.
authors: Miho
authors: M
authors: Nakamichi
authors: Department of Pathology, School of Medicine, Toho University, Tokyo, Japan.
authors: Yuri
authors: Y
authors: Akishima-Fukasawa
authors: Division of Research Promotion and Development, Advanced Research Center, Toho University, Tokyo, Japan.
authors: Chie
authors: C
authors: Fujisawa
authors: Department of Pathology, School of Medicine, Toho University, Tokyo, Japan.
authors: Tetuo
authors: T
authors: Mikami
authors: Department of Plastic and Reconstructive Surgery, Toho University Omori Medical Center, Tokyo, Japan.
authors: Kiyoshi
authors: K
authors: Onishi
authors: Department of Pathology, School of Medicine, Toho University, Tokyo, Japan; Regenerative Disease Research Unit, Advanced Research Center, Toho University, Tokyo, Japan. Electronic address: akasakay@med.toho-u.ac.jp.
authors: Yoshikiyo
authors: Y
authors: Akasaka
mesh_terms: D043925:Angiogenesis Inducing Agents; D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D003239:Connective Tissue Cells / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*; D000098853:Podoplanin
chemical_list: D043925:Angiogenesis Inducing Agents; D018952:Antigens, CD34; D024042:Collagen Type I; D016222:Fibroblast Growth Factor 2; D017493:Leukocyte Common Antigens; D008562:Membrane Glycoproteins; D011347:Procollagen; D042461:Vascular Endothelial Growth Factor A; C117468:PDPN protein, human; D000098853:Podoplanin; C467484:VEGFA protein, human; C516769:PTPRC protein, human