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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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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. |
format | Online Article Text |
id | pubmed-9278565 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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