Estrogen Receptors alpha/beta promote liver regeneration through hepatic progenitor differentiation in mice

• Main Authors: Ta-Lun Kao, 高大倫
• Other Authors: Wen-Lung Ma
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/v7y8n6

碩士 === 中國醫藥大學 === 臨床醫學研究所碩士班 === 101 === Introduction: The scarcity of donor organs has created a disparity between the supply and demand in liver transplantation. Both the recipients and the donors must rely on the regeneration capacity of liver regeneration (LR). The quality of LR relies on hepatocytes, cholangiocytes, and other residing cells to form functional hepatic units that orchestrated in certain manner. Hormonal feminization was reported in LR that raised the curiosity of estrogen and its receptors (ER alpha and ER beta) functions in LR processes. Methods: Bilirubin levels reduction after liver transplantation surgery (marker for liver function recovery) was analyzed in patients (donors and recipients) of a hospital-based cohort. In vivo 2/3 partial hepatectomy (PHx) were performed in wildtype, ER alpha and ER beta knockout transgenes mice to observe LR activity, histology, and proliferation marker gene expressions. In vitro studies using human hepatic progenitor cells (HepRG) treated with 17 beta-estrodiol (E2), PPT or DPN (ER alpha and ER beta agonists) to examine cell growth, cell cycle, and cell differentiation marker genes. Result: The latency of bilirubin levels reduction was faster in women than men. The LR activities were impaired in ER alpha and ER beta knockouts mice compared to their wildtype littermates. We observed comparable serum E2 levels in WT(wild type) vs. ERs (Estrogen receptors) knockout mice, indicating an essential role of both ERs in LR. We found little impact of estrogenic signals on cell growth by comparing cell proliferation marker (Ki-67) in WT vs. ERs knockout, as well as treatments of E2, PPT, or DPN on HepRG cells growth. However, treating E2, PPT, or DPN could increase hepatocyte and cholangiocyte differentiation markers in the HepRG cells. At last, E2, PPT, and DPN could upregulate HNF4 alpha (hepatic progenitor transcription factor) expressions that provided mechanistic insight to estrogenic function in LR. Conclusion: This is the first report to describe E2/ERs signaling in LR. Our study would bring improvement for patient management of poor liver function or small-for–size liver grafts surgery.