TNF-α regulates mouse fetal hepatic maturation induced by oncostatin M and extracellular matrices
✍ Scribed by Akihide Kamiya; Frank J. Gonzalez
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 693 KB
- Volume
- 40
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
Fetal hepatic maturation consists of multisteps and is regulated by several cytokines and cell-cell or cell-matrices interactions. In the mid-to-late fetal stage, hepatocytes have few metabolic functions associated with adult liver homeostasis. Cultured fetal hepatocytes acquire the expression of several mature liver-specific genes through stimulation with hepatic maturation factor oncostatin M (OSM) and matrigel. Tumor necrosis factor-␣ (TNF␣) regulates fetal hepatic maturation stimulated by OSM and matrigel. TNF␣ suppressed expression of mature liver-specific genes such as tyrosine aminotransferase and apolipoproteins. In addition, the expression of hematopoietic cytokines and cyclin A2, repressed by OSM and matrigel, is induced by TNF␣ in the fetal hepatic cultures coincident with cell division. TNF␣ inhibited the induction of hepatocyte nuclear factor 4␣ induced by OSM and matrigel, suggesting that down-regulation of hepatocyte nuclear factor 4␣ expression is involved in the mechanism of suppression of hepatic maturation by TNF␣. Interestingly, TNF␣ is expressed in the prenatal and postnatal liver but not in adult liver, whereas TNFR1, a TNF␣ receptor, is expressed in both fetal and adult livers. In conclusion, TNF␣ is a suppressive factor of hepatic maturation. The balance between hepatic maturation factor (OSM and extracellular matrices) and TNF␣ is important for liver development.