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Título: | Experimental acute pancreatitis in PAP/HIP knock-out mice |
Autor: | Gironella, Meritxell; Folch-Puy, Emma CSIC ORCID ; Closa, Daniel CSIC ORCID; Iovanna, Juan Lucio | Fecha de publicación: | 2007 | Editor: | BMJ Publishing Group | Citación: | Gut 56(8): 1091-1097 (2007) | Resumen: | [Background and aims]: PAP/HIP was first reported as an additional pancreatic secretory protein expressed during the acute phase of pancreatitis. It was shown in vitro to be anti-apoptotic and anti-inflammatory. This study aims to look at whether PAP/HIP plays the same role in vivo. [Methods]: A model of caerulein-induced pancreatitis was used to compare the outcome of pancreatitis in PAP/HIP-/- and wild-type mice. [Results]: PAP/HIP-/- mice showed the normal phenotype at birth and normal postnatal development. Caerulein-induced pancreatic necrosis was, however, less severe in PAP/HIP -/- mice than in wild-type mice, as judged by lower amylasemia and lipasemia levels and smaller areas of necrosis. On the contrary, pancreas from PAP/HIP-/- mice was more sensitive to apoptosis, in agreement with the anti-apoptotic effect of PAP/HIP in vitro. Surprisingly, pancreatic inflammation was more extensive in PAP/HIP-/- mice, as judged from histological parameters, increased myeloperoxidase activity and increased pro-inflammatory cytokine expression. This result, in apparent contradiction with the limited necrosis observed in these mice, is, however, in agreement with the anti-inflammatory function previously reported in vitro for PAP/HIP. This is supported by the observation that activation of the STAT3/SOCS3 pathway was strongly decreased in the pancreas of PAP/HIP-/- mice and by the reversion of the apoptotic and inflammatory phenotypes upon administration of recombinant PAP/HIP to PAP/HIP-/- mice. [Conclusion]: The anti-apoptotic and anti-inflammatory functions described in vitro for PAP/HIP have physiological relevance in the pancreas in vivo during caerulein-induced pancreatitis. | Versión del editor: | http://dx.doi.org/10.1136/gut.2006.116087 | URI: | http://hdl.handle.net/10261/89375 | DOI: | 10.1136/gut.2006.116087 | Identificadores: | doi: 10.1136/gut.2006.116087 issn: 0017-5749 e-issn: 1468-3288 |
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