Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon-tetrachloride-induced liver fibrosis in mice.
We previously reported that fibroblast growth factor 2 (FGF2) facilitated the differentiation of transplanted bone marrow cells (BMCs) into hepatocytes. Our earlier study also demonstrated that administration of FGF2 in combination with bone marrow transplantation (BMT) synergistically activated tumor necrosis factor-alpha signaling and significantly improved liver function and prognosis more than BMT alone. However, the way that it affected the extracellular matrix remained unclear. Here, we investigated the effect of FGF2 treatment together with BMT on liver fibrosis in mice treated with carbon tetrachloride (CCl(4)). Transplantation of BMCs and concurrent treatment with FGF2 caused a statistically significant reduction in CCl(4)-induced liver fibrosis that was accompanied by strong expression of matrix metalloproteinase 9 as compared with FGF2-only treatment or BMT alone. Moreover, in this process, the proliferation of bone-marrow-derived cells was accelerated without causing apoptosis. Thus, the administration of FGF2 in combination with BMT synergistically improves CCl(4)-induced liver fibrosis in mice. This treatment has the potential of being an effective therapy for patients with liver cirrhosis.
Ishikawa
Tsuyoshi
T
Department of Molecular Science and Applied Medicine, Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan. terais@yamaguchi-u.ac.jp
Terai
Shuji
S
Urata
Yohei
Y
Marumoto
Yoshio
Y
Aoyama
Koji
K
Murata
Tomoaki
T
Mizunaga
Yuko
Y
Yamamoto
Naoki
N
Nishina
Hiroshi
H
Shinoda
Koh
K
Sakaida
Isao
I
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
D019394:Ki-67 Antigen; D016222:Fibroblast Growth Factor 2; D020780:Matrix Metalloproteinase 9