Abstract
Culturing fetal hepatocytes in high cell-density allowed stabilization of the hepatocyte phenotype up to 8 weeks, including the maintenance of liver-specific functions. On the other hand, when cultured at low cell-density, fetal hepatocytes underwent morphological modifications and acquired fibroblastic morphology. Since a switch from E-cadherin to vimentin expression accompanied these changes, we hypothesized the occurrence of epithelial-to-mesenchymal transition when fetal hepatocytes were cultured at low cell-density. Changes in gene expressionsuch as up-regulation of fibrosis-related geneswere also observed, suggesting that the low cell-density culture system promoted the acquisition of a profibrotic phenotype in cultured hepatocytes. The origin of fibrogenic cells in the liver is not well known, and the role of hepatocytes as a source of fibrogenic cells is controversial. Therefore, we hypothesized that hepatocytes undergoing epithelial-to-mesenchymal transition could have a central role in liver fibrosis as a source of fibrogenic cells. To conclude, the high cell-density culture system could be a useful model for in vitro studies requiring long-term cultures of hepatocytes, such as the development of pharmaceutical drugs and mechanisms of viral infections. The low cell-density culture system may provide additional insights into the origin of fibrogenic cells in the liver, thus contributing to the development of novel therapeutic approaches.
| Original language | English |
|---|---|
| Pages (from-to) | 472-479 |
| Number of pages | 8 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 490 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Aug 19 2017 |
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Keywords
- Epithelial to mesenchymal transition
- Fetal hepatocytes
- Liver fibrosis
- Primary cultures
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
In vitro evidences of epithelial to mesenchymal transition in low cell-density cultured human fetal hepatocytes. / Chinnici, Cinzia Maria; Miceli, Vitale; Pampalone, Mariangela; Lo Nigro, Antonio; Amico, Giandomenico; Conaldi, Pier Giulio.
In: Biochemical and Biophysical Research Communications, Vol. 490, No. 2, 19.08.2017, p. 472-479.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In vitro evidences of epithelial to mesenchymal transition in low cell-density cultured human fetal hepatocytes
AU - Chinnici, Cinzia Maria
AU - Miceli, Vitale
AU - Pampalone, Mariangela
AU - Lo Nigro, Antonio
AU - Amico, Giandomenico
AU - Conaldi, Pier Giulio
PY - 2017/8/19
Y1 - 2017/8/19
N2 - Culturing fetal hepatocytes in high cell-density allowed stabilization of the hepatocyte phenotype up to 8 weeks, including the maintenance of liver-specific functions. On the other hand, when cultured at low cell-density, fetal hepatocytes underwent morphological modifications and acquired fibroblastic morphology. Since a switch from E-cadherin to vimentin expression accompanied these changes, we hypothesized the occurrence of epithelial-to-mesenchymal transition when fetal hepatocytes were cultured at low cell-density. Changes in gene expressionsuch as up-regulation of fibrosis-related geneswere also observed, suggesting that the low cell-density culture system promoted the acquisition of a profibrotic phenotype in cultured hepatocytes. The origin of fibrogenic cells in the liver is not well known, and the role of hepatocytes as a source of fibrogenic cells is controversial. Therefore, we hypothesized that hepatocytes undergoing epithelial-to-mesenchymal transition could have a central role in liver fibrosis as a source of fibrogenic cells. To conclude, the high cell-density culture system could be a useful model for in vitro studies requiring long-term cultures of hepatocytes, such as the development of pharmaceutical drugs and mechanisms of viral infections. The low cell-density culture system may provide additional insights into the origin of fibrogenic cells in the liver, thus contributing to the development of novel therapeutic approaches.
AB - Culturing fetal hepatocytes in high cell-density allowed stabilization of the hepatocyte phenotype up to 8 weeks, including the maintenance of liver-specific functions. On the other hand, when cultured at low cell-density, fetal hepatocytes underwent morphological modifications and acquired fibroblastic morphology. Since a switch from E-cadherin to vimentin expression accompanied these changes, we hypothesized the occurrence of epithelial-to-mesenchymal transition when fetal hepatocytes were cultured at low cell-density. Changes in gene expressionsuch as up-regulation of fibrosis-related geneswere also observed, suggesting that the low cell-density culture system promoted the acquisition of a profibrotic phenotype in cultured hepatocytes. The origin of fibrogenic cells in the liver is not well known, and the role of hepatocytes as a source of fibrogenic cells is controversial. Therefore, we hypothesized that hepatocytes undergoing epithelial-to-mesenchymal transition could have a central role in liver fibrosis as a source of fibrogenic cells. To conclude, the high cell-density culture system could be a useful model for in vitro studies requiring long-term cultures of hepatocytes, such as the development of pharmaceutical drugs and mechanisms of viral infections. The low cell-density culture system may provide additional insights into the origin of fibrogenic cells in the liver, thus contributing to the development of novel therapeutic approaches.
KW - Epithelial to mesenchymal transition
KW - Fetal hepatocytes
KW - Liver fibrosis
KW - Primary cultures
UR - http://www.scopus.com/inward/record.url?scp=85020787165&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020787165&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2017.06.065
DO - 10.1016/j.bbrc.2017.06.065
M3 - Article
C2 - 28624456
AN - SCOPUS:85020787165
VL - 490
SP - 472
EP - 479
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -