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H19 Is Expressed in Hybrid Hepatocyte Nuclear Factor 4?+ Periportal Hepatocytes but Not Cytokeratin 19+ Cholangiocytes in Cholestatic Livers.


ABSTRACT: 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. H19RNA+ 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 H19RNA+/sex-determining region Y (SRY)-box 9 (SOX9)+ ductal progenitor cells, H19RNA+/hepatocyte nuclear factor 4? (HNF4?)+ hepatocytes, H19RNA+/F4/80+ Kupffer cells, HNF4?+/SOX9+ hybrid hepatocytes, as well as triple-positive H19 RNA+/HNF4?+/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: H19RNA is localized in HNF4?+ periportal hepatocytes, SOX9+ ductal progenitor cells, and F4/80+ Kupffer cells but not in CK19+ cholangiocytes and desmin+ stellate cells in cholestatic livers.

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC6211330 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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H19 Is Expressed in Hybrid Hepatocyte Nuclear Factor 4α<sup>+</sup> Periportal Hepatocytes but Not Cytokeratin 19<sup>+</sup> Cholangiocytes in Cholestatic Livers.

Jiang YanChao Y   Huang Yi Y   Cai ShiYing S   Song YongFeng Y   Boyer James L JL   Zhang KeZhong K   Gao Ling L   Zhao JiaJun J   Huang WenDong W   Liang Guang G   Liangpunsakul Suthat S   Wang Li L  

Hepatology communications 20180924 11


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 <b><i>in situ</i></b> 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 w  ...[more]

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