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Activity of acute pancreatitis is modified by secreted protein acidic and rich in cysteine ablation

BACKGROUND: Acute pancreatitis (AP) is a frequent cause for hospitalization. However, molecular determinants that modulate severity of experimental pancreatitis are only partially understood. OBJECTIVE: To investigate the role of secreted protein acidic and rich in cysteine (SPARC) during cerulein‐i...

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Autores principales: Ammer‐Herrmenau, Christoph, Wolf, Laurin, Nasrin, Syeda S., Ramu, Iswarya, Roggiolani, Roberta, Goetze, Robert G., Buchholz, Soeren M., Sendler, Mathias, Ellenrieder, Volker, Neesse, Albrecht
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278565/
https://www.ncbi.nlm.nih.gov/pubmed/35699570
http://dx.doi.org/10.1002/ueg2.12262
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author Ammer‐Herrmenau, Christoph
Wolf, Laurin
Nasrin, Syeda S.
Ramu, Iswarya
Roggiolani, Roberta
Goetze, Robert G.
Buchholz, Soeren M.
Sendler, Mathias
Ellenrieder, Volker
Neesse, Albrecht
author_facet Ammer‐Herrmenau, Christoph
Wolf, Laurin
Nasrin, Syeda S.
Ramu, Iswarya
Roggiolani, Roberta
Goetze, Robert G.
Buchholz, Soeren M.
Sendler, Mathias
Ellenrieder, Volker
Neesse, Albrecht
author_sort Ammer‐Herrmenau, Christoph
collection PubMed
description BACKGROUND: Acute pancreatitis (AP) is a frequent cause for hospitalization. However, molecular determinants that modulate severity of experimental pancreatitis are only partially understood. OBJECTIVE: To investigate the role of secreted protein acidic and rich in cysteine (SPARC) during cerulein‐induced AP in mice. METHODS: AP was induced by repeated cerulein injections in SPARC knock‐out mice (SPARC(−/−)) and control littermates (SPARC(+/+)). Secreted protein acidic and rich in cysteine expression and severity of AP were determined by histopathological scoring, immunohistochemistry, and biochemical assays. For functional analysis, primary murine acinar cell cultures with subsequent amylase release assays were employed. Proteome profiler assay and ELISA were conducted from pancreatic tissue lysates, and co‐immunofluorescence was performed. RESULTS: Upon cerulein induction, SPARC expression was robustly induced in pancreatic stellate cells (PSCs) but not in acinar cells. Genetic SPARC ablation resulted in attenuated severity of AP with significantly reduced levels of pancreatic necrosis, apoptosis, immune cell infiltration, and reduced fibrosis upon chronic stimulation. However, the release of amylase upon cerulein stimulation in primary acinar cell culture from SPARC(+/+) and SPARC(−/−) was indistinguishable. Notably, immune cell derived C‐C Motif Chemokine Ligand 2 (CCL2) was highly elevated in SPARC(+/+) pancreatic tissue potentially linking PSC derived SPARC with CCL2 induction in AP. CONCLUSION: SPARC mediates the severity of AP. The potential link between SPARC and the CCL2 axis could open new avenues for tailored therapeutic interventions in AP patients and warrants further investigations.
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spelling pubmed-92785652022-07-15 Activity of acute pancreatitis is modified by secreted protein acidic and rich in cysteine ablation Ammer‐Herrmenau, Christoph Wolf, Laurin Nasrin, Syeda S. Ramu, Iswarya Roggiolani, Roberta Goetze, Robert G. Buchholz, Soeren M. Sendler, Mathias Ellenrieder, Volker Neesse, Albrecht United European Gastroenterol J Pancreas BACKGROUND: Acute pancreatitis (AP) is a frequent cause for hospitalization. However, molecular determinants that modulate severity of experimental pancreatitis are only partially understood. OBJECTIVE: To investigate the role of secreted protein acidic and rich in cysteine (SPARC) during cerulein‐induced AP in mice. METHODS: AP was induced by repeated cerulein injections in SPARC knock‐out mice (SPARC(−/−)) and control littermates (SPARC(+/+)). Secreted protein acidic and rich in cysteine expression and severity of AP were determined by histopathological scoring, immunohistochemistry, and biochemical assays. For functional analysis, primary murine acinar cell cultures with subsequent amylase release assays were employed. Proteome profiler assay and ELISA were conducted from pancreatic tissue lysates, and co‐immunofluorescence was performed. RESULTS: Upon cerulein induction, SPARC expression was robustly induced in pancreatic stellate cells (PSCs) but not in acinar cells. Genetic SPARC ablation resulted in attenuated severity of AP with significantly reduced levels of pancreatic necrosis, apoptosis, immune cell infiltration, and reduced fibrosis upon chronic stimulation. However, the release of amylase upon cerulein stimulation in primary acinar cell culture from SPARC(+/+) and SPARC(−/−) was indistinguishable. Notably, immune cell derived C‐C Motif Chemokine Ligand 2 (CCL2) was highly elevated in SPARC(+/+) pancreatic tissue potentially linking PSC derived SPARC with CCL2 induction in AP. CONCLUSION: SPARC mediates the severity of AP. The potential link between SPARC and the CCL2 axis could open new avenues for tailored therapeutic interventions in AP patients and warrants further investigations. John Wiley and Sons Inc. 2022-06-14 /pmc/articles/PMC9278565/ /pubmed/35699570 http://dx.doi.org/10.1002/ueg2.12262 Text en © 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Pancreas
Ammer‐Herrmenau, Christoph
Wolf, Laurin
Nasrin, Syeda S.
Ramu, Iswarya
Roggiolani, Roberta
Goetze, Robert G.
Buchholz, Soeren M.
Sendler, Mathias
Ellenrieder, Volker
Neesse, Albrecht
Activity of acute pancreatitis is modified by secreted protein acidic and rich in cysteine ablation
title Activity of acute pancreatitis is modified by secreted protein acidic and rich in cysteine ablation
title_full Activity of acute pancreatitis is modified by secreted protein acidic and rich in cysteine ablation
title_fullStr Activity of acute pancreatitis is modified by secreted protein acidic and rich in cysteine ablation
title_full_unstemmed Activity of acute pancreatitis is modified by secreted protein acidic and rich in cysteine ablation
title_short Activity of acute pancreatitis is modified by secreted protein acidic and rich in cysteine ablation
title_sort activity of acute pancreatitis is modified by secreted protein acidic and rich in cysteine ablation
topic Pancreas
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278565/
https://www.ncbi.nlm.nih.gov/pubmed/35699570
http://dx.doi.org/10.1002/ueg2.12262
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