Steatohepatitis/Metabolic Liver Disease

Hepatic progenitor cells activation, fibrosis, and adipokines production in pediatric nonalcoholic fatty liver disease†‡

  1. Valerio Nobili1,§,
  2. Guido Carpino2,§,
  3. Anna Alisi1,
  4. Antonio Franchitto3,4,
  5. Gianfranco Alpini5,
  6. Rita De Vito6,
  7. Paolo Onori7,
  8. Domenico Alvaro4,8,
  9. Eugenio Gaudio3,¶,*

Article first published online: 4 DEC 2012

DOI: 10.1002/hep.25742

Issue

Hepatology

Hepatology

Volume 56, Issue 6, pages 2142–2153, December 2012

Additional Information

How to Cite

Nobili, V., Carpino, G., Alisi, A., Franchitto, A., Alpini, G., De Vito, R., Onori, P., Alvaro, D. and Gaudio, E. (2012), Hepatic progenitor cells activation, fibrosis, and adipokines production in pediatric nonalcoholic fatty liver disease. Hepatology, 56: 2142–2153. doi: 10.1002/hep.25742

Author Information

  1. 1

    Unit of Liver Research, Bambino Gesù Children's Hospital, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy

  2. 2

    Department of Health Sciences, University of Rome “Foro Italico,” Rome, Italy

  3. 3

    Department of Anatomical, Histological, Forensic Medicine, and Orthopedic Sciences, Sapienza University of Rome, Rome, Italy

  4. 4

    Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy

  5. 5

    Division of Research, Central Texas Veterans Health Care System, Department of Medicine, Scott & White Digestive Disease Research Center, Scott & White and Texas A&M Health Science Center College of Medicine, Temple, TX

  6. 6

    Unit of Pathology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy

  7. 7

    Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy

  8. 8

    Department of Sciences and Medical and Surgical Biotechnologies, Sapienza University of Rome, Rome, Italy

  1. §

    These authors contributed equally to this work.

  2. fax: +39.06.4991.8062

*Department of Human Anatomy, Histology, Forensic Medicine, and Orthopedics, Sapienza University of Rome, Via Borelli 50, 00161 Rome, Italy

  1. †

    Potential conflict of interest: Nothing to report.

  2. ‡

    E.G. was supported by a research project grant from the University “Sapienza” of Rome (Rome, Italy) (Fondo per gli Investimenti della Ricerca di Base [FIRB] grant no. RBAP10Z7FS_001 and by Research Program for the Development of Research of National Interest [PRIN] grant no. 2009X84L84_001). D.A. was supported by FIRB grant no. RBAP10Z7FS_004 and by PRIN grant no. 2009X84L84_002).

  3. §

    These authors contributed equally to this work.

  4. fax: +39.06.4991.8062

Publication History

  1. Issue published online: 4 DEC 2012
  2. Article first published online: 4 DEC 2012
  3. Accepted manuscript online: 29 MAR 2012 06:16AM EST
  4. Manuscript Accepted: 19 MAR 2012
  5. Manuscript Received: 22 NOV 2011

Funded by

  • University “Sapienza” of Rome (Rome, Italy)
  • Fondo per gli Investimenti della Ricerca di Base [FIRB]. Grant Number: RBAP10Z7FS_001
  • Development of Research of National Interest [PRIN]. Grant Number: 2009X84L84_001
  • FIRB. Grant Number: RBAP10Z7FS_004
  • PRIN. Grant Number: 2009X84L84_002

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Additional Supporting Information may be found in the online version of this article.

FilenameFormatSizeDescription
HEP_25742_sm_SuppFig1.tif5768KSupporting Information Figure 1. Immunohistochemistry for adiponectin in normal and steatotic livers (pediatric non-alcoholic fatty liver disease [pNAFLD]). This image provides additional information about adiponectin positivity in endothelial cells and steatotic hepatocytes. In normal and steatotic livers, adiponectin is also expressed by the endothelial cells (arrows) of the hepatic artery branches (A) and hepatic sinusoids (B). In steatotic livers, hepatocytes with steatosis express adiponectin (arrows in C).
HEP_25742_sm_SuppFig2.tif4081KSupporting Information Figure 2. Figure S2. Separate channels of double immunofluorescence for cytokeratin-7 (CK-7; green) and adiponectin (red) in pNAFLD. Nuclei were counterstained with 4′,6-diamidino-2-phenylindole (DAPI) and are shown in blue. As indicated by the white arrows, the cells (fibroblasts or hepatocytes) around reactive ductules are clearly negative for both antigens, confirming that the positivity is specifically restricted to hepatic progenitor cells (HPCs; yellow arrows) in reactive ductules. Notably, the positivity in several HPCs is localized to an inner position (see the arrows in the separate channels), in which 2 CK-7-positive HPCs face each other; this aspect further supports the evidence that the CK7-positive HPCs are truly positive for this adipokine and excludes the possibility that the positivity derives from the bleeding of color from closely adjacent cells into HPCs.
HEP_25742_sm_SuppFig3.tif5047KSupporting Information Figure 3. Figure S3. Separate channels of double immunofluorescence for CK-7 (green) and resistin (red) in pNAFLD. Nuclei were counterstained with DAPI and are shown in blue. As indicated by the white arrows, the cells (fibroblasts or hepatocytes) around reactive ductules are clearly negative for both antigens, confirming that the positivity is specifically restricted to HPCs (yellow arrows) in reactive ductules. Notably, the positivity in several HPCs is localized to an inner position (see the arrows in the separate channels), in which 2 CK7-positive HPCs face each other; this aspect further supports the evidence that the CK7-positive HPCs are truly positive for this adipokine and excludes the possibility that the positivity derives from the bleeding of color from closely adjacent cells into HPCs.
HEP_25742_sm_SuppFig4.tif5654KSupporting Information Figure 4. Figure S4. Separate channels of double Immunofluorescence for CK-7 (green) and glucagon-like peptide 1 (GLP-1; red) in pNAFLD. Nuclei were counterstained with DAPI and are shown in blue. As indicated by the white arrows, the cells (fibroblasts or hepatocytes) around reactive ductules are clearly negative for both antigens, confirming that the positivity is specifically restricted to HPCs (yellow arrows) in reactive ductules. Notably, the positivity in several HPCs is localized to an inner position (see the arrows in the separate channels), in which 2 CK7-positive HPCs face each other; this aspect further supports the evidence that the CK7-positive HPCs are truly positive for this adipokine and excludes the possibility that the positivity derives from the bleeding of color from closely adjacent cells into HPCs.
HEP_25742_sm_SuppInfo.doc32KSupporting Information

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