PMID- 17093919 OWN - NLM STAT- MEDLINE DCOM- 20070501 LR - 20070208 IS - 0302-766X (Print) IS - 0302-766X (Linking) VI - 327 IP - 3 DP - 2007 Mar TI - Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon-tetrachloride-induced liver fibrosis in mice. PG - 463-70 AB - 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. FAU - Ishikawa, Tsuyoshi AU - Ishikawa T AD - 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 FAU - Terai, Shuji AU - Terai S FAU - Urata, Yohei AU - Urata Y FAU - Marumoto, Yoshio AU - Marumoto Y FAU - Aoyama, Koji AU - Aoyama K FAU - Murata, Tomoaki AU - Murata T FAU - Mizunaga, Yuko AU - Mizunaga Y FAU - Yamamoto, Naoki AU - Yamamoto N FAU - Nishina, Hiroshi AU - Nishina H FAU - Shinoda, Koh AU - Shinoda K FAU - Sakaida, Isao AU - Sakaida I LA - eng PT - Journal Article DEP - 20061109 PL - Germany TA - Cell Tissue Res JT - Cell and tissue research JID - 0417625 RN - 0 (Ki-67 Antigen) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Apoptosis/drug effects MH - *Bone Marrow Transplantation MH - Cell Proliferation/drug effects MH - Combined Modality Therapy MH - Female MH - Fibroblast Growth Factor 2/*therapeutic use MH - Fluorescent Antibody Technique, Indirect MH - In Situ Nick-End Labeling MH - Ki-67 Antigen/metabolism MH - Liver/drug effects/enzymology/*pathology MH - Liver Cirrhosis, Experimental/*drug therapy/pathology/*surgery MH - Matrix Metalloproteinase 9/metabolism MH - Mice MH - Mice, Inbred C57BL EDAT- 2006/11/10 09:00 MHDA- 2007/05/02 09:00 CRDT- 2006/11/10 09:00 PHST- 2006/01/23 00:00 [received] PHST- 2006/08/18 00:00 [accepted] PHST- 2006/08/11 00:00 [revised] PHST- 2006/11/10 09:00 [pubmed] PHST- 2007/05/02 09:00 [medline] PHST- 2006/11/10 09:00 [entrez] AID - 10.1007/s00441-006-0334-x [doi] PST - ppublish SO - Cell Tissue Res. 2007 Mar;327(3):463-70. doi: 10.1007/s00441-006-0334-x. Epub 2006 Nov 9.