Bone marrow–derived cells express matrix metalloproteinases and contribute to regression of liver fibrosis in mice

• DOI: 10.1002/hep.21477
• Publication Date: 2006-12-22T23:19:52Z
• Authors: Reiichi Higashiyama; Yutaka Inagaki; Yun Yu Hong; Miwa Kushida; Sachie Nakao; Maki Niioka; Tetsu Watanabe; Hideyuki Okano; Yumi Matsuzaki; Goshi Shiota; Isao Okazaki
• Keywords: Hepatic stellate cell

Liver fibrosis is usually progressive, but it can occasionally be reversible if the causative agents are adequately removed or patients treated effectively. However, molecular mechanisms responsible for this reversibility of liver have been poorly understood. To reveal contribution bone marrow (BM)-derived cells to spontaneous regression fibrosis, mice were with repeated carbon tetrachloride injections after hematopoietic reconstitution enhanced green fluorescent protein (EGFP)-expressing BM cells. The distribution and characteristics EGFP-positive (EGFP(+)) present in fibrotic tissue examined at different time points cessation intoxication. A large number EGFP(+) observed peak which decreased during recovery from fibrosis. Some them, as well EGFP-negative (EGFP(-)) resident cells, expressed matrix metalloproteinase (MMP)-13 MMP-9. Whereas MMP-13 was transiently mainly clustering periportal areas, MMP-9 expression enzymatic activity detected over resolution process several kinds located portal areas along fibrous septa. Therapeutic recruitment by granulocyte colony-stimulating factor (G-CSF) treatment significantly migration BM-derived into accelerated Experiments using transgenic overexpressing hepatocyte growth (HGF) indicated that G-CSF HGF synergistically increased septa.Autologous contribute their therapeutic derivation could a new strategy intractable