Tamoxifen affects chronic pancreatitis‐related fibrogenesis in an experimental mouse model: an effect beyond Cre recombination
Tamoxifen is very successfully used for the induction of CreERT‐mediated genomic recombination in conditional mouse models. Recent studies, however, indicated that tamoxifen might also affect the fibrotic response in several disease models following administration, both in vitro and in vivo. In orde...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2019-10-01
|
Series: | FEBS Open Bio |
Subjects: | |
Online Access: | https://doi.org/10.1002/2211-5463.12714 |
id |
doaj-225c54fd55d5443192b93992134c1b3f |
---|---|
record_format |
Article |
spelling |
doaj-225c54fd55d5443192b93992134c1b3f2020-11-25T03:37:43ZengWileyFEBS Open Bio2211-54632019-10-019101756176810.1002/2211-5463.12714Tamoxifen affects chronic pancreatitis‐related fibrogenesis in an experimental mouse model: an effect beyond Cre recombinationXuan Li0Christian Clappier1Ingo Kleiter2Rainer Heuchel3Pancreas Cancer Research (PaCaRes) Lab Department of Clinical Science, Intervention and Technology Karolinska Institutet Stockholm SwedenPancreas Cancer Research (PaCaRes) Lab Department of Clinical Science, Intervention and Technology Karolinska Institutet Stockholm SwedenDepartment of Neurology Ruhr‐Universität Bochum GermanyPancreas Cancer Research (PaCaRes) Lab Department of Clinical Science, Intervention and Technology Karolinska Institutet Stockholm SwedenTamoxifen is very successfully used for the induction of CreERT‐mediated genomic recombination in conditional mouse models. Recent studies, however, indicated that tamoxifen might also affect the fibrotic response in several disease models following administration, both in vitro and in vivo. In order to investigate a possible effect of tamoxifen on pancreatic fibrogenesis and to evaluate an optimal treatment scheme in an experimental pancreatitis mouse model, we administered tamoxifen by oral gavage to both male and female C57BL/6J mice and then waited for different periods of time before inducing chronic pancreatitis by cerulein. We observed a sex‐specific and time‐dependent effect of tamoxifen on the fibrotic response as measured by collagen deposition and the number of myofibroblasts and macrophages. The findings of in vitro studies, in which cerulein was administrated with or without 4‐hydroxytamoxifen to stimulate primary murine female and male pancreatic stellate cells, supported our in vivo observations. Real‐time PCR also indicated that this effect may be related to differences in ERα expression between female and male stellate cells. Our data demonstrate that tamoxifen administration has unignorable side effects, which affect the experimental outcome in a cerulein‐based model of chronic pancreatitis in mice. We suggest a 2‐week waiting period before cerulein administration to reduce side effects to a minimum for the described fibrosis model in female mice.https://doi.org/10.1002/2211-5463.12714Cre‐LoxPfibrosispancreatitistamoxifen |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xuan Li Christian Clappier Ingo Kleiter Rainer Heuchel |
spellingShingle |
Xuan Li Christian Clappier Ingo Kleiter Rainer Heuchel Tamoxifen affects chronic pancreatitis‐related fibrogenesis in an experimental mouse model: an effect beyond Cre recombination FEBS Open Bio Cre‐LoxP fibrosis pancreatitis tamoxifen |
author_facet |
Xuan Li Christian Clappier Ingo Kleiter Rainer Heuchel |
author_sort |
Xuan Li |
title |
Tamoxifen affects chronic pancreatitis‐related fibrogenesis in an experimental mouse model: an effect beyond Cre recombination |
title_short |
Tamoxifen affects chronic pancreatitis‐related fibrogenesis in an experimental mouse model: an effect beyond Cre recombination |
title_full |
Tamoxifen affects chronic pancreatitis‐related fibrogenesis in an experimental mouse model: an effect beyond Cre recombination |
title_fullStr |
Tamoxifen affects chronic pancreatitis‐related fibrogenesis in an experimental mouse model: an effect beyond Cre recombination |
title_full_unstemmed |
Tamoxifen affects chronic pancreatitis‐related fibrogenesis in an experimental mouse model: an effect beyond Cre recombination |
title_sort |
tamoxifen affects chronic pancreatitis‐related fibrogenesis in an experimental mouse model: an effect beyond cre recombination |
publisher |
Wiley |
series |
FEBS Open Bio |
issn |
2211-5463 |
publishDate |
2019-10-01 |
description |
Tamoxifen is very successfully used for the induction of CreERT‐mediated genomic recombination in conditional mouse models. Recent studies, however, indicated that tamoxifen might also affect the fibrotic response in several disease models following administration, both in vitro and in vivo. In order to investigate a possible effect of tamoxifen on pancreatic fibrogenesis and to evaluate an optimal treatment scheme in an experimental pancreatitis mouse model, we administered tamoxifen by oral gavage to both male and female C57BL/6J mice and then waited for different periods of time before inducing chronic pancreatitis by cerulein. We observed a sex‐specific and time‐dependent effect of tamoxifen on the fibrotic response as measured by collagen deposition and the number of myofibroblasts and macrophages. The findings of in vitro studies, in which cerulein was administrated with or without 4‐hydroxytamoxifen to stimulate primary murine female and male pancreatic stellate cells, supported our in vivo observations. Real‐time PCR also indicated that this effect may be related to differences in ERα expression between female and male stellate cells. Our data demonstrate that tamoxifen administration has unignorable side effects, which affect the experimental outcome in a cerulein‐based model of chronic pancreatitis in mice. We suggest a 2‐week waiting period before cerulein administration to reduce side effects to a minimum for the described fibrosis model in female mice. |
topic |
Cre‐LoxP fibrosis pancreatitis tamoxifen |
url |
https://doi.org/10.1002/2211-5463.12714 |
work_keys_str_mv |
AT xuanli tamoxifenaffectschronicpancreatitisrelatedfibrogenesisinanexperimentalmousemodelaneffectbeyondcrerecombination AT christianclappier tamoxifenaffectschronicpancreatitisrelatedfibrogenesisinanexperimentalmousemodelaneffectbeyondcrerecombination AT ingokleiter tamoxifenaffectschronicpancreatitisrelatedfibrogenesisinanexperimentalmousemodelaneffectbeyondcrerecombination AT rainerheuchel tamoxifenaffectschronicpancreatitisrelatedfibrogenesisinanexperimentalmousemodelaneffectbeyondcrerecombination |
_version_ |
1724544259396206592 |