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Matrix metalloproteinase-14 mediates formation of bile ducts and hepatic maturation of fetal hepatic progenitor cells
- Source :
- Biochemical and biophysical research communications. 469(4)
- Publication Year :
- 2015
-
Abstract
- Fetal hepatic stem/progenitor cells, called hepatoblasts, play central roles in liver development; however, the molecular mechanisms regulating the phenotype of these cells have not been completely elucidated. Matrix metalloproteinase (MMP)-14 is a type I transmembrane proteinase regulating pericellular proteolysis of the extracellular matrix and is essential for the activation of several MMPs and cytokines. However, the physiological functions of MMP-14 in liver development are unknown. Here we describe a functional role for MMP-14 in hepatic and biliary differentiation of mouse hepatoblasts. MMP-14 was upregulated in cells around the portal vein in perinatal stage liver. Formation of bile duct-like structures in MMP-14-deficient livers was significantly delayed compared with wild-type livers in vivo. In vitro biliary differentiation assays showed that formation of cholangiocytic cysts derived from MMP-14-deficient hepatoblasts was completely impaired, and that overexpression of MMP-14 in hepatoblasts promoted the formation of bile duct-like cysts. In contrast, the expression of molecules associated with metabolic functions in hepatocytes, including hepatic nuclear factor 4α and tryptophan 2,3-dioxygenase, were significantly increased in MMP-14-deficient livers. Expression of the epidermal growth factor receptor and phosphorylation of mitogen-activated protein kinases were significantly upregulated in MMP-14-deficient livers. We demonstrate that MMP-14-mediated signaling in fetal hepatic progenitor cells promotes biliary luminal formation around the portal vein and negatively controls the maturation of hepatocytes.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Cellular differentiation
Biophysics
Biology
Matrix metalloproteinase
Biochemistry
Extracellular matrix
03 medical and health sciences
Mice
Internal medicine
medicine
Matrix Metalloproteinase 14
Animals
Progenitor cell
Molecular Biology
Cells, Cultured
Cell Proliferation
Mice, Knockout
Stem Cells
Lymphokine
Cell Differentiation
Cell Biology
Cell biology
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
Liver
Biliary tract
Mitogen-activated protein kinase
biology.protein
Bile Ducts
Stem cell
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 469
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....dda3aee82231dc8353791a09e13385df