The Expression of E-cadherin in Human and Rat Hepatic Stellate Cells: Evidence of Epithelial-Mesenchymal Transition

Lim, Young Suk; Lee, Hyo Suk

Abstract

BACKGROUND/AIMS: 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.