HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice
Open Access
- 22 August 2005
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 42 (3), 618-626
- https://doi.org/10.1002/hep.20845
Abstract
Human hepatocarcinoma-intestine-pancreas/pancreatic-associated protein HIP/PAP is a secreted C-type lectin belonging to group VII, according to Drickamer's classification. HIP/PAP is overexpressed in liver carcinoma; however, its functional role remains unclear. In this study, we demonstrate that HIP/PAP is a paracrine hepatic growth factor promoting both proliferation and viability of liver cells in vivo. First, a low number of implanted hepatocytes deriving from HIP/PAP-transgenic mice (<1:1,000) was sufficient to stimulate overall recipient severe combined immunodeficiency liver regeneration after partial hepatectomy. After a single injection of HIP/PAP protein, the percentages of bromodeoxyuridine-positive nuclei and mitosis were statistically higher than after saline injection, indicating that HIP/PAP acts as a paracrine mitogenic growth factor for the liver. Comparison of the early events posthepatectomy in control and transgenic mice indicated that HIP/PAP accelerates the accumulation/degradation of nuclear phospho–signal transducer activator transcription factor 3 and tumor necrosis factor α level, thus reflecting that HIP/PAP accelerates liver regeneration. Second, we showed that 80% of the HIP/PAP-transgenic mice versus 25% of the control mice were protected against lethal acetaminophen-induced fulminate hepatitis. A single injection of recombinant HIP/PAP induced a similar cytoprotective effect, demonstrating the antiapoptotic effect of HIP/PAP. Comparison of Cu/Zn superoxide dismutase activity and glutathione reductase-like effects in control and transgenic liver mice indicated that HIP/PAP exerts an antioxidant activity and prevents reactive oxygen species-induced mitochondrial damage by acetaminophen overdose. In conclusion, the present data offer new insights into the biological functions of C-type lectins. In addition, HIP/PAP is a promising candidate for the prevention and treatment of liver failure. (HEPATOLOGY 2005;42:618–626.)This publication has 37 references indexed in Scilit:
- HIP/PAP, a C‐type lectin overexpressed in hepatocellular carcinoma, binds the RIIα regulatory subunit of cAMP‐dependent protein kinase and alters the cAMP‐dependent protein kinase signallingJBIC Journal of Biological Inorganic Chemistry, 2004
- INGAP peptide improves nerve function and enhances regeneration in streptozotocin‐induced diabetic C57BL/6 miceThe FASEB Journal, 2004
- Small-for-size liver syndrome after auxiliary and split liver transplantation: Donor selectionLiver Transplantation, 2003
- Hepatocyte growth factor gene therapy accelerates regeneration in cirrhotic mouse livers after hepatectomyGut, 2003
- Liver regenerationJournal of Hepatology, 2000
- C-type lectin-like domainsCurrent Opinion in Structural Biology, 1999
- Cell adhesion in the process of asexual reproduction of tunicatesMicroscopy Research and Technique, 1999
- Plasma clearance, tissue uptake and expression of pituitary peptide 23/pancreatitis-associated protein in the ratJournal of Endocrinology, 1995
- The human HIP gene, overexpressed in primary liver cancer encodes for a C‐type carbohydrate binding protein with lactose binding activityFEBS Letters, 1994
- Efficacy of Oral N-Acetylcysteine in the Treatment of Acetaminophen OverdoseNew England Journal of Medicine, 1988