Article

Digestive Diseases and Sciences

, Volume 48, Issue 4, pp 717-725

First online:

Up-Regulation of p75 Neurotrophin Receptor (p75NTR) Is Associated with Apoptosis in Chronic Pancreatitis

  • Zhaowen ZhuAffiliated withDepartment of General Surgery, University of Heidelberg
  • , Helmut FriessAffiliated withDepartment of General Surgery, University of Heidelberg
  • , Xin ShiAffiliated withDepartment of General Surgery, University of Heidelberg
  • , Li WangAffiliated withDepartment of General Surgery, University of Heidelberg
  • , Francesco F. Di MolaAffiliated withDepartment of General Surgery, University of Heidelberg
  • , Martin WirtzAffiliated withDepartment of General Surgery, University of Heidelberg
  • , Mark HartelAffiliated withDepartment of General Surgery, University of Heidelberg
  • , Markus WagnerAffiliated withDepartment of Visceral and Transplantation Surgery, University of Bern
  • , Arthur ZimmermannAffiliated withInstitute of Pathology, University of Bern
    • , Michael MüllerAffiliated withDepartment of General Surgery, University of Heidelberg
    • , Markus W. BüchlerAffiliated withDepartment of General Surgery, University of Heidelberg

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Abstract

Activation of apoptosis in chronic pancreatitis has been demonstrated. The low-affinity neurotrophin receptor p75 (p75NTR) mediates apoptosis in many cell types in vivo and in vitro. The aim of this study was to examine whether p75NTR is involved in the apoptotic process in chronic pancreatitis. The quantity and localization of the receptor was evaluated using northern blot analysis, in situ hybridization, immunohistochemistry, and western blot analysis. Apoptosis was determined by TUNEL assay. By northern blot analysis, p75NTR mRNA levels were increased 40-fold in chronic pancreatitis compared with normal pancreas (P < 0.01). in situ hybridization revealed weak p75NTR mRNA expression in some ductal cells in the normal pancreas. In contrast in chronic pancreatitis moderate p75NTR expression was present in acinar cells next to fibrosis, ductal cells, and cells of ductular structures as well as in some islet cells. Immunostaining of p75NTR in normal pancreas and chronic pancreatitis tissue samples showed a similar intensity and distribution pattern as found by in situ hybridization. Higher p75NTR protein levels could be confirmed by western blot analysis, which revealed an 8.6-fold increase of p75NTR in chronic pancreatitis. TUNEL staining showed, in chronic pancreatitis samples, positivity in some acinar cells next to fibrosis, some ductal cells, and cells of ductular structures. Also some islet cells were positive by TUNEL staining. The presence of p75NTR immunoreactivity was positively correlated (P < 0.05) with the apoptotic index in the exocrine and endocrine pancreas. In conclusion, p75NTR, the low-affinity receptor of neurotrophins which mediates apoptosis, is up-regulated in CP and is involved in the apoptotic process of the exocrine and endocrine pancreas.

p75NTR chronic pancreatitis apoptosis TUNEL assay