Basic Fibroblast Growth Factor Induces Angiogenic Properties of Fibrocytes to Stimulate Vascular Formation during Wound Healing

• Published in: The American journal of pathology Vol. 186; no. 12; pp. 3203 - 3216
• Main Authors: Nakamichi, Miho, Akishima-Fukasawa, Yuri, Fujisawa, Chie, Mikami, Tetsuo, Onishi, Kiyoshi, Akasaka, Yoshikiyo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2016
• Subjects: Angiogenesis Inducing Agents; Animals; Antigens, CD34 - genetics; Antigens, CD34 - metabolism; Capillaries - metabolism; Cell Proliferation; Cells, Cultured; Collagen Type I - genetics; Collagen Type I - metabolism; Connective Tissue Cells - physiology; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - metabolism; Fibroblasts - physiology; Leukocyte Common Antigens - genetics; Leukocyte Common Antigens - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Pathology; Procollagen - genetics; Procollagen - metabolism; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Wound Healing - physiology
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/j.ajpath.2016.08.015

The precise role of fibrocytes in angiogenesis in wounds 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 markedly 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, markedly 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 highlighted the angiogenic properties of CD34+ /procollagen I+ fibrocytes specifically induced by bFGF, which provides new insight into the active contribution of fibrocytes for vascular formation during wound healing.