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

Jiang, Yanchao; Huang, Yi Wen; Cai, Shi‐Ying; Song, Yuelin; Boyer, James L.; Zhang, Kezhong; Gao, Ling; Zhao, Jiajun; Huang, Wendong; Liang, Guang; Liangpunsakul, Suthat; Wang, Li

doi:10.1002/hep4.1252

Cited by 13 publications

(12 citation statements)

References 41 publications

(77 reference statements)

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“…The group of H. Zhou found that in the liver of young Mdr2-KO females, H19 was expressed mainly in the cholangiocytes with minor expression in hepatocytes [17]. In contrast, the group of L. Wang demonstrated that in the liver of middle-aged Mdr2-KO females, H19 was expressed mainly in hepatocytes (with minor expression in Kupffer cells) [21]. In both these studies, the Mdr2-KO mice were of the FVB/N genetic Fig.…”

Section: Liver Cells That Express H19mentioning

confidence: 98%

The pro-oncogenic effect of the lncRNA H19 in the development of chronic inflammation-mediated hepatocellular carcinoma

et al. 2020

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The oncofetal long noncoding RNA (lncRNA) H19 is postnatally repressed in most tissues, and re-expressed in many cancers, including hepatocellular carcinoma (HCC). The role of H19 in carcinogenesis is a subject of controversy. We aimed to examine the role of H19 in chronic inflammation-mediated hepatocarcinogenesis using the Mdr2/Abcb4 knockout (Mdr2-KO) mouse, a well-established HCC model. For this goal, we have generated Mdr2-KO/H19-KO double knockout (dKO) mice and followed spontaneous tumor development in the dKO and control Mdr2-KO mice. Cellular localization of H19 and effects of H19 loss in the liver were determined in young and old Mdr2-KO mice. Tumor incidence and tumor load were both significantly decreased in the liver of dKO versus Mdr2-KO females. The expression levels of H19 and Igf2 were variable in nontumor liver tissues of Mdr2-KO females and were significantly downregulated in most matched tumors. In nontumor liver tissue of aged Mdr2-KO females, H19 was expressed mainly in hepatocytes, and hepatocyte proliferation was increased compared to dKO females. At an early age, dKO females displayed lower levels of liver injury and B-cell infiltration, with higher percentage of binuclear hepatocytes. In human samples, H19 expression was higher in females, positively correlated with cirrhosis (in nontumor liver samples) and negatively correlated with CTNNB1 (beta-catenin) mutations and patients' survival (in tumors). Our data demonstrate that the lncRNA H19 is pro-oncogenic during the development of chronic inflammation-mediated HCC in the Mdr2-KO mouse model, mainly by increasing liver injury and decreasing hepatocyte polyploidy in young mice.

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Section: Liver Cells That Express H19mentioning

confidence: 98%

The pro-oncogenic effect of the lncRNA H19 in the development of chronic inflammation-mediated hepatocellular carcinoma

et al. 2020

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“…Briefly, samples were fixed with 4% of formaldehyde for 2 hours at RT, followed by protease IV digestion for 30 minutes to remove proteins including nucleases. The previously characterized H19 probe 42,43 and CD31 probe were mixed and added to the slides to hybridize for 2 hours at 40°C in a HybEz oven (Advanced Cell Diagnostic Inc), followed by signal amplification and washing steps, and mounted with VECTASHIELD Mounting medium (H-5000). Hybridization signals were detected by red and green chromogens for CD31 and H19, respectively.…”

Section: If and Rna In Situ Hybridizationmentioning

confidence: 99%

H19/TET1 axis promotes TGF‐β signaling linked to endothelial‐to‐mesenchymal transition

Cao

Jiang

et al. 2020

FASEB j.

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While emerging evidence suggests the link between endothelial activation of TGF‐β signaling, induction of endothelial‐to‐mesenchymal transition (EndMT), and cardiovascular disease (CVD), the molecular underpinning of this connection remains enigmatic. Here, we report aberrant expression of H19 lncRNA and TET1 in endothelial cells (ECs) of human atherosclerotic coronary arteries. Using primary human umbilical vein endothelial cells (HUVECs) and aortic endothelial cells (HAoECs) we show that TNF‐α, a known risk factor for endothelial dysfunction and CVD, induces H19 expression which in turn activates TGF‐β signaling and EndMT via a TET1‐dependent epigenetic mechanism. We also show that H19 regulates TET1 expression at the posttranscriptional level. Further, we provide evidence that this H19/TET1‐mediated regulation of TGF‐β signaling and EndMT occurs in mouse pulmonary microvascular ECs in vivo under hyperglycemic conditions. We propose that endothelial activation of the H19/TET1 axis may play an important role in EndMT and perhaps CVD.

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“…129 On the other hand, H19 upregulates EpCAM and Sox9 expression that can be crucial for HPC. Recent studies on the role of H19 in cholestatic liver injury [130][131][132][133] demonstrated that H19 þ cell population is rather heterogeneous and can drive the process. However, the question whether these cells have intrinsic stem cell-like potential or they are just intermediates between HPC and hepatoblasts or mature parenchymal cells is still open.…”

Section: Lncrna In Liver Regenerationmentioning

confidence: 99%

Noncoding RNA in Liver Regeneration—From Molecular Mechanisms to Clinical Implications

2019

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The unique ability of the adult liver to regenerate after injury is the basis for efficient surgical resection and liver transplantation and provides solutions for the treatment of liver cancer and acute liver failure. Current success in surgical treatments could be enhanced by directed regulation of liver regeneration. A number of small molecules and growth factors have been tested in mice models to improve liver regeneration. Noncoding ribonucleic acids (ncRNA) are less studied regulators of various cellular processes. Here, the authors carefully review ncRNA involved in liver regeneration and discuss molecular mechanisms and regulatory networks. These ncRNAs modulate the expression of pro- and antiproliferative genes allowing to orchestrate precisely the proliferation of hepatocytes. The authors expect that ncRNA will become new targets in liver regeneration due to recent progress in therapeutic nucleic acids. Among a large number of preclinical studies on ncRNA, only a few entered clinical trials, and further studies are needed to uncover their potential as therapeutic targets.

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

Cited by 13 publications

References 41 publications

The pro-oncogenic effect of the lncRNA H19 in the development of chronic inflammation-mediated hepatocellular carcinoma

The pro-oncogenic effect of the lncRNA H19 in the development of chronic inflammation-mediated hepatocellular carcinoma

H19/TET1 axis promotes TGF‐β signaling linked to endothelial‐to‐mesenchymal transition

Noncoding RNA in Liver Regeneration—From Molecular Mechanisms to Clinical Implications

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