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Calcineurin B1 Deficiency Reduces Proliferation, Increases Apoptosis, and Alters Secretion in Enteric Glial Cells of Mouse Small Intestine in Culture
To investigate the roles of calcineurin (CN) in glial cells, we previously generated conditional knockout (CKO) mice lacking CNB1 in glial cells. Because these CKO mice showed dysfunction and inflammation of the small intestine in addition to growth impairment and postweaning death, we have focused...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10378349/ https://www.ncbi.nlm.nih.gov/pubmed/37508531 http://dx.doi.org/10.3390/cells12141867 |
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author | Teramoto, Hikaru Hirashima, Naohide Tanaka, Masahiko |
author_facet | Teramoto, Hikaru Hirashima, Naohide Tanaka, Masahiko |
author_sort | Teramoto, Hikaru |
collection | PubMed |
description | To investigate the roles of calcineurin (CN) in glial cells, we previously generated conditional knockout (CKO) mice lacking CNB1 in glial cells. Because these CKO mice showed dysfunction and inflammation of the small intestine in addition to growth impairment and postweaning death, we have focused on enteric glial cells (EGCs) in the small intestine. In this study, we examined the effects of CNB1 deficiency on the proliferation and survival of EGCs and the expression and secretion of EGC-derived substances in culture to reveal the mechanisms of how CNB1 deficiency leads to dysfunction and inflammation of the small intestine. In primary myenteric cultures of the small intestine, EGCs from the CKO mice showed reduced proliferation and increased apoptosis compared with EGCs from control mice. In purified EGC cultures from the CKO mice, Western blot analysis showed increased expression of S100B, iNOS, GFAP, and GDNF, and increased phosphorylation of NF-κB p65. In the supernatants of purified EGC cultures from the CKO mice, ELISA showed reduced secretion of TGF-β1. In contrast, GDNF secretion was not altered in purified EGC cultures from the CKO mice. Furthermore, treatment with an S100B inhibitor partially rescued the CKO mice from growth impairment and postweaning death in vivo. In conclusion, CNB1 deficiency leads to reduced proliferation and increased apoptosis of EGCs and abnormal expression and secretion of EGC-derived substances, which may contribute to dysfunction and inflammation of the small intestine. |
format | Online Article Text |
id | pubmed-10378349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103783492023-07-29 Calcineurin B1 Deficiency Reduces Proliferation, Increases Apoptosis, and Alters Secretion in Enteric Glial Cells of Mouse Small Intestine in Culture Teramoto, Hikaru Hirashima, Naohide Tanaka, Masahiko Cells Article To investigate the roles of calcineurin (CN) in glial cells, we previously generated conditional knockout (CKO) mice lacking CNB1 in glial cells. Because these CKO mice showed dysfunction and inflammation of the small intestine in addition to growth impairment and postweaning death, we have focused on enteric glial cells (EGCs) in the small intestine. In this study, we examined the effects of CNB1 deficiency on the proliferation and survival of EGCs and the expression and secretion of EGC-derived substances in culture to reveal the mechanisms of how CNB1 deficiency leads to dysfunction and inflammation of the small intestine. In primary myenteric cultures of the small intestine, EGCs from the CKO mice showed reduced proliferation and increased apoptosis compared with EGCs from control mice. In purified EGC cultures from the CKO mice, Western blot analysis showed increased expression of S100B, iNOS, GFAP, and GDNF, and increased phosphorylation of NF-κB p65. In the supernatants of purified EGC cultures from the CKO mice, ELISA showed reduced secretion of TGF-β1. In contrast, GDNF secretion was not altered in purified EGC cultures from the CKO mice. Furthermore, treatment with an S100B inhibitor partially rescued the CKO mice from growth impairment and postweaning death in vivo. In conclusion, CNB1 deficiency leads to reduced proliferation and increased apoptosis of EGCs and abnormal expression and secretion of EGC-derived substances, which may contribute to dysfunction and inflammation of the small intestine. MDPI 2023-07-17 /pmc/articles/PMC10378349/ /pubmed/37508531 http://dx.doi.org/10.3390/cells12141867 Text en © 2023 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 Teramoto, Hikaru Hirashima, Naohide Tanaka, Masahiko Calcineurin B1 Deficiency Reduces Proliferation, Increases Apoptosis, and Alters Secretion in Enteric Glial Cells of Mouse Small Intestine in Culture |
title | Calcineurin B1 Deficiency Reduces Proliferation, Increases Apoptosis, and Alters Secretion in Enteric Glial Cells of Mouse Small Intestine in Culture |
title_full | Calcineurin B1 Deficiency Reduces Proliferation, Increases Apoptosis, and Alters Secretion in Enteric Glial Cells of Mouse Small Intestine in Culture |
title_fullStr | Calcineurin B1 Deficiency Reduces Proliferation, Increases Apoptosis, and Alters Secretion in Enteric Glial Cells of Mouse Small Intestine in Culture |
title_full_unstemmed | Calcineurin B1 Deficiency Reduces Proliferation, Increases Apoptosis, and Alters Secretion in Enteric Glial Cells of Mouse Small Intestine in Culture |
title_short | Calcineurin B1 Deficiency Reduces Proliferation, Increases Apoptosis, and Alters Secretion in Enteric Glial Cells of Mouse Small Intestine in Culture |
title_sort | calcineurin b1 deficiency reduces proliferation, increases apoptosis, and alters secretion in enteric glial cells of mouse small intestine in culture |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10378349/ https://www.ncbi.nlm.nih.gov/pubmed/37508531 http://dx.doi.org/10.3390/cells12141867 |
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