Collagens in the liver extracellular matrix bind hepatocyte growth factor

Schuppan, Detlef; Schmid, Monika S.; Somasundaram, Rajan; Ackermann, Renate; Ruehl, Martin; Nakamura, Toshikazu; Riecken, Ernst–Otto

doi:10.1016/s0016-5085(98)70642-0

Cited by 148 publications

(102 citation statements)

References 45 publications

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“…However, HGF is also reported to bind collagens within the liver ECM. 46 Our results indicated that expression of MMP-2, -9, -13, and -14 was induced after PH, and these MMPs are known to process collagens. 5 Michalopoulos' group has shown that HGF activation in regenerating rat liver occurs in two phases, a consumptive phase and a productive phase.…”

Section: Discussionsupporting

confidence: 50%

Metalloproteinase inhibitor TIMP-1 affects hepatocyte cell cycle via HGF activation in murine liver regeneration

et al. 2005

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Section: Discussionsupporting

confidence: 50%

Metalloproteinase inhibitor TIMP-1 affects hepatocyte cell cycle via HGF activation in murine liver regeneration

et al. 2005

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“…A similar scheme has been suggested for TGF-␤ and was recently shown for hepatocyte growth factor. 28 Associated with labeling of the extracellular matrix, significant staining was also observed in spindle cells located either in the fibrous septa and in the lobule. Since myofibroblasts and activated HSC are the major sources of extracellular matrix components in the liver, the cellular origin of HSC was suspected.…”

Section: Discussionmentioning

confidence: 97%

Expression of connective tissue growth factor in experimental rat and human liver fibrosis

et al. 1999

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Connective tissue growth factor (CTGF) stimulates in vitro fibroblast proliferation and extracellular matrix synthesis. The aim of this study was to assess the role of CTGF in liver fibrogenesis. CTGF expression was investigated both at the protein and mRNA level in biopsies of chronic liver diseases, in experimental models of liver fibrosis, and in hepatic stellate cells in culture. CTGF immunostaining was observed in most human liver biopsies with significant fibrosis. An increase of CTGF immunostaining was associated with a higher score of fibrosis both in the group of chronic hepatitis C ( 2 ‫؍‬ 9.3; P F .01) and in the non-hepatitis C group ( 2 ‫؍‬ 7.2; P F .02). In situ hybridization showed CTGF mRNA expression in spindle cells in both the fibrous septa and sinusoidal lining. In experimental models of liver fibrosis, CTGF accumulated in parallel with the development of septal fibrosis and cirrhosis. Quantification of CTGF mRNA by a real-time reversetranscription polymerase chain reaction (RT-PCR) assay showed a significant increase of CTGF mRNA in both CCl 4 -induced and bile duct-ligated rat models of liver fibrosis. Expression of CTGF protein and mRNA was definitively assigned to hepatic stellate cells, because CTGF was detected by Western blot both in lysate and supernatant of a hepatic stellate cell line derived from rats. These cells also displayed CTGF protein and mRNA as shown by immunohistochemistry and in situ hybridization. In conclusion, this study shows that CTGF is strongly expressed during liver fibrogenesis, and hepatic stellate cells seem to be the major cellular sources of CTGF in the liver. (HEPATOL-OGY 1999;30:968-976.)

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“…HGF has substantial affinity for different types of collagen and collagen-bound HGF is biologically active [30]. Thus, the mixture of type-1 collagen and b-TCP was expected to provide a biodegradable scaffold for local delivery of HGF.…”

Section: Discussionmentioning

confidence: 99%

Repair of segmental bone defects in rabbit tibia promoted by a complex of β-tricalcium phosphate and hepatocyte growth factor

Goshima

Nakase

et al. 2012

Journal of Orthopaedic Science

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Background Segmental bone defect repair remains a clinical and scientific challenge with increasing interest focused on bone tissue engineering. Clinical studies are ongoing to address application of hepatocyte growth factor (HGF) for treatment of some diseases; however, the use of HGF in bone tissue engineering has not been addressed. This study was performed to evaluate the effect of HGF in a complex of b-tricalcium phosphate (b-TCP) and collagen in repairing segmental bone defects. Methods Segmental bone defects 5 mm long were created in the middle of the tibial shafts of rabbits. The defect was stabilized with external fixators and implanted with a complex of b-TCP granules and collagen, with or without 100 lg recombinant human HGF. Biweekly, bone regeneration and b-TCP resorption were assessed radiographically and histologically. At 4 and 8 weeks, bone regeneration was evaluated by use of micro-computed tomography and mechanical tests. Results Compared with the bone tissue treated with b-TCP and collagen, mineralization, angiogenesis, new bone formation, and absorption of b-TCP were promoted 4 weeks postoperatively by treatment with HGF in the b-TCP and collagen group. These changes were associated with promoting biomechanical regeneration. By 8 weeks, the formation of bone marrow in newly generated bone and absorption of the b-TCP granules were completed in a shorter period by combining HGF with b-TCP and collagen, compared with tissues without HGF. Conclusions The combined application of HGF in a b-TCP and collagen matrix promoted histological bone healing and augmented mechanical strength of the healing bone, particularly in the early stages. The combined use of HGF and b-TCP for treatment of bone defects made a substantial difference.

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Collagens in the liver extracellular matrix bind hepatocyte growth factor

Cited by 148 publications

References 45 publications

Metalloproteinase inhibitor TIMP-1 affects hepatocyte cell cycle via HGF activation in murine liver regeneration

Metalloproteinase inhibitor TIMP-1 affects hepatocyte cell cycle via HGF activation in murine liver regeneration

Expression of connective tissue growth factor in experimental rat and human liver fibrosis

Repair of segmental bone defects in rabbit tibia promoted by a complex of β-tricalcium phosphate and hepatocyte growth factor

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