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The Rabep1-Mediated Endocytosis and Activation of Trypsinogen to Promote Pancreatic Stellate Cell Activation

Background: The pathogenesis of chronic pancreatitis is still unclear. Trypsinogen activation is an active factor in acute pancreatitis that has not been studied in the occurrence of chronic pancreatitis. Methods: Immunofluorescence was used to detect the location and expression of trypsinogen in ch...

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Autores principales: Yao, Wenchao, Luo, Dankun, Lv, Zhenyi, Yang, Yang, Wang, Liyi, Ma, Biao, Xue, Dongbo, Hao, Chenjun, Zhang, Yingmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406084/
https://www.ncbi.nlm.nih.gov/pubmed/36008957
http://dx.doi.org/10.3390/biom12081063
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author Yao, Wenchao
Luo, Dankun
Lv, Zhenyi
Yang, Yang
Wang, Liyi
Ma, Biao
Xue, Dongbo
Hao, Chenjun
Zhang, Yingmei
author_facet Yao, Wenchao
Luo, Dankun
Lv, Zhenyi
Yang, Yang
Wang, Liyi
Ma, Biao
Xue, Dongbo
Hao, Chenjun
Zhang, Yingmei
author_sort Yao, Wenchao
collection PubMed
description Background: The pathogenesis of chronic pancreatitis is still unclear. Trypsinogen activation is an active factor in acute pancreatitis that has not been studied in the occurrence of chronic pancreatitis. Methods: Immunofluorescence was used to detect the location and expression of trypsinogen in chronic pancreatitis and normal tissues. Microarray and single-cell RNA-seq (scRNA-seq) were used to screen core genes and pathways in pancreatic stellate cells (PSCs). Western blotting and immunofluorescence were used to verify trypsinogen expression in PSCs after silencing Rabep1. Immunofluorescence and flow cytometry were used to validate trypsinogen activation and PSC activation after intervening in the endocytosis pathway. Results: Endocytosed trypsinogen was found in PSCs in CP clinical samples. Bioinformatic analysis showed that Rabep1 is a core gene that regulates trypsinogen endocytosis through the endocytosis pathway, verified by Western blot and immunofluorescence. Immunofluorescence and flow cytometry analyses confirmed the activation of trypsinogen and PSCs through the endocytosis pathway in PSCs. Conclusion: This study discovered a new mechanism by which trypsinogen affects the activation of PSCs and the occurrence and development of CP. Through communication between pancreatic acinar cells and PSCs, trypsinogen can be endocytosed by PSCs and activated by the Rabep1 gene.
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spelling pubmed-94060842022-08-26 The Rabep1-Mediated Endocytosis and Activation of Trypsinogen to Promote Pancreatic Stellate Cell Activation Yao, Wenchao Luo, Dankun Lv, Zhenyi Yang, Yang Wang, Liyi Ma, Biao Xue, Dongbo Hao, Chenjun Zhang, Yingmei Biomolecules Article Background: The pathogenesis of chronic pancreatitis is still unclear. Trypsinogen activation is an active factor in acute pancreatitis that has not been studied in the occurrence of chronic pancreatitis. Methods: Immunofluorescence was used to detect the location and expression of trypsinogen in chronic pancreatitis and normal tissues. Microarray and single-cell RNA-seq (scRNA-seq) were used to screen core genes and pathways in pancreatic stellate cells (PSCs). Western blotting and immunofluorescence were used to verify trypsinogen expression in PSCs after silencing Rabep1. Immunofluorescence and flow cytometry were used to validate trypsinogen activation and PSC activation after intervening in the endocytosis pathway. Results: Endocytosed trypsinogen was found in PSCs in CP clinical samples. Bioinformatic analysis showed that Rabep1 is a core gene that regulates trypsinogen endocytosis through the endocytosis pathway, verified by Western blot and immunofluorescence. Immunofluorescence and flow cytometry analyses confirmed the activation of trypsinogen and PSCs through the endocytosis pathway in PSCs. Conclusion: This study discovered a new mechanism by which trypsinogen affects the activation of PSCs and the occurrence and development of CP. Through communication between pancreatic acinar cells and PSCs, trypsinogen can be endocytosed by PSCs and activated by the Rabep1 gene. MDPI 2022-07-31 /pmc/articles/PMC9406084/ /pubmed/36008957 http://dx.doi.org/10.3390/biom12081063 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yao, Wenchao
Luo, Dankun
Lv, Zhenyi
Yang, Yang
Wang, Liyi
Ma, Biao
Xue, Dongbo
Hao, Chenjun
Zhang, Yingmei
The Rabep1-Mediated Endocytosis and Activation of Trypsinogen to Promote Pancreatic Stellate Cell Activation
title The Rabep1-Mediated Endocytosis and Activation of Trypsinogen to Promote Pancreatic Stellate Cell Activation
title_full The Rabep1-Mediated Endocytosis and Activation of Trypsinogen to Promote Pancreatic Stellate Cell Activation
title_fullStr The Rabep1-Mediated Endocytosis and Activation of Trypsinogen to Promote Pancreatic Stellate Cell Activation
title_full_unstemmed The Rabep1-Mediated Endocytosis and Activation of Trypsinogen to Promote Pancreatic Stellate Cell Activation
title_short The Rabep1-Mediated Endocytosis and Activation of Trypsinogen to Promote Pancreatic Stellate Cell Activation
title_sort rabep1-mediated endocytosis and activation of trypsinogen to promote pancreatic stellate cell activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406084/
https://www.ncbi.nlm.nih.gov/pubmed/36008957
http://dx.doi.org/10.3390/biom12081063
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