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Ptf1a inactivation in adult pancreatic acinar cells causes apoptosis through activation of the endoplasmic reticulum stress pathway
- Source :
- Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018), Scientific Reports
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Pancreas transcription factor 1 subunit alpha (PTF1A) is one of the key regulators in pancreatogenesis. In adults, it transcribes digestive enzymes, but its other functions remain largely unknown. Recent conditional knockout studies using Ptf1aCreER/floxed heterozygous mouse models have found PTF1A contributes to the identity maintenance of acinar cells and prevents tumorigenesis caused by the oncogenic gene Kras. However, Ptf1a heterozygote is known to behave differently from homozygote. To elucidate the effects of Ptf1a homozygous loss, we prepared Elastase-CreERTM; Ptf1afloxed/floxed mice and found that homozygous Ptf1a deletion in adult acinar cells causes severe apoptosis. Electron microscopy revealed endoplasmic reticulum (ER) stress, a known cause of unfolded protein responses (UPR). We confirmed that UPR was upregulated by the activating transcription factor 6 (ATF6) and protein kinase RNA (PKR)-like endoplasmic reticulum kinase (PERK) pathways, but not the inositol requiring enzyme 1 (IRE1) pathway. Furthermore, we detected the expression of CCAAT-enhancer-binding protein (C/EBP) homologous protein (CHOP), a pro-apoptotic factor, indicating the apoptosis was induced through UPR. Our homozygous model helps clarify the role PTF1A has on the homeostasis and pathogenesis of exocrine pancreas in mice.
- Subjects :
- X-Box Binding Protein 1
0301 basic medicine
RNA Splicing
Science
Activating transcription factor
Apoptosis
Acinar Cells
Biology
Endoplasmic Reticulum
C/EBP Homologous Protein (CHOP)
Article
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Conditional gene knockout
Animals
Cell Lineage
Adult Acinar Cells
RNA, Messenger
Protein kinase A
Transcription factor
Mice, Knockout
Multidisciplinary
ATF6
Endoplasmic reticulum
Endoplasmic Reticulum Stress
Inositol-requiring Enzyme 1 (IRE1)
Protein kinase R
Pancreas, Exocrine
Activating Transcription Factor 6
Up-Regulation
Cell biology
030104 developmental biology
030220 oncology & carcinogenesis
ATF6 Pathway
Medicine
IRE1 Pathway
Transcription Factor CHOP
Transcription Factors
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....ed1b22fe4f626dbb2834debec4b9f98c