[The expression of E-cadherin in human and rat hepatic stellate cells: evidence of epithelial-mesenchymal transition].
OBJECTIVE
The embryonal origin of hepatic stellate cells (HSCs), the principal cells in hepatic fibrogenesis, is still intriguing. We have previously demonstrated that human HSCs express cytokeratins which suggests the epithelial origin of these cells. To further explore the origin and the differentiation of HSCs we studied the expression of E-cadherin, the specific marker of epithelial cells, in human and rat HSCs.


METHODS
We studied the changing pattern of E-cadherin expression during spontaneous activation of primarily isolated human HSCs by immunofluorescence staining and RT-PCR. To confirm the expression of E-cadherin in HSCs in vivo we performed double immunofluorescence staining for E-cadherin and glial fibrillary acidic protein, the specific identification marker of quiescent rat HSCs, in normal rat liver.


RESULTS
Quiescent human HSCs were labeled strongly by anti-E-cadherin monoclonal antibody at the first and seventh days after primary culture. Human HSCs, however, did not stain for E-cadherin after the first passage of culture. RT-PCR also confirmed these modulations of E-cadherin expression. Double immunofluorescence staining, performed on rat liver tissue and observed by confocal laser scanning microscopy, unequivocally revealed the membranous expression of E-cadherin in quiescent HSCs labeled by glial fibrillary acidic protein.


CONCLUSIONS
Quiescent HSCs of humans and rats express E-cadherin both in vitro and in vivo. The extent of E-cadherin expression rapidly decreases during the process of spontaneous activation. Our results suggest that HSCs may be of epithelial origin and undergo epithelial-mesenchymal transition during activation process.
Lim
Young Suk
YS
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. hsleemd@snu.ac.kr
Lee
Hyo Suk
HS
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015820:Cadherins; D005904:Glial Fibrillary Acidic Protein