Open AccessH19 Is Expressed in Hybrid Hepatocyte Nuclear Factor 4α + Periportal Hepatocytes but Not Cytokeratin 19 + Cholangiocytes in Cholestatic Livers
Author(s) -
Jiang YanChao,
Huang Yi,
Cai ShiYing,
Song YongFeng,
Boyer James L.,
Zhang KeZhong,
Gao Ling,
Zhao JiaJun,
Huang WenDong,
Liang Guang,
Liangpunsakul Suthat,
Wang Li
Publication year - 2018
Publication title -
hepatology communications
Language(s) - English
Resource type - Journals
ISSN - 2471-254X
DOI - 10.1002/hep4.1252
Subject(s) - hepatocyte , cholestasis , biology , cytokeratin , pathology , progenitor cell , hepatocyte nuclear factor 4 , hepatic stellate cell , bile duct , primary sclerosing cholangitis , microbiology and biotechnology , medicine , stem cell , endocrinology , transcription factor , immunohistochemistry , gene , nuclear receptor , biochemistry , disease , in vitro
Long noncoding RNA (lncRNA) H19 is abundantly expressed in fetal liver. Its expression is significantly diminished in adult healthy liver but is re‐induced in chronic liver diseases, including cholestasis. In this study, we developed a new method with combined in situ hybridization (ISH) and immunofluorescence (IF) colabeling to establish an H19 expression profile with both parenchymal and nonparenchymal cell‐specific markers in the livers of cholestatic mouse models and patients with cholestasis. H19 RNA + cells showed no colocalization with biliary epithelial cell marker cytokeratin 19 (CK19) + cholangiocytes but were immediately adjacent to biliary structures in bile duct ligation (BDL), 3,5‐diethoxycarbony1‐1,4‐dihydrocollidine (DDC), and multidrug‐resistant gene 2 knockout ( Mdr2 –/– ) mouse models and in human primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) liver specimens. In contrast, double‐positive H19 RNA + /sex‐determining region Y (SRY)‐box 9 (SOX9) + ductal progenitor cells, H19 RNA + /hepatocyte nuclear factor 4α (HNF4α) + hepatocytes, H19 RNA + /F4/80 + Kupffer cells, HNF4α + /SOX9 + hybrid hepatocytes, as well as triple‐positive H19 RNA + /HNF4α + /SOX9 + periportal hepatocytes were identified. In addition, H19 RNA could not be detected in mesenchymal cell marker desmin + cells. Furthermore, H19 RNA was predominately detected in cytoplasm with a small amount at the interspace with neighboring cells. Conclusion: H19 RNA is localized in HNF4α + periportal hepatocytes, SOX9 + ductal progenitor cells, and F4/80 + Kupffer cells but not in CK19 + cholangiocytes and desmin + stellate cells in cholestatic livers.