XBP1 controls maturation of gastric zymogenic cells by induction of MIST1 and expansion of the rough endoplasmic reticulum.

10:48 EDT 28th August 2015 | BioPortfolio

Summary of "XBP1 controls maturation of gastric zymogenic cells by induction of MIST1 and expansion of the rough endoplasmic reticulum."

BACKGROUND &
AIMS:
: The transition of gastric epithelial mucous neck cells (NCs) to digestive-enzyme-secreting zymogenic cells (ZCs) involves an increase in rough endoplasmic reticulum (rER) and formation of many large secretory vesicles. The transcription factor MIST1 is required for granulogenesis of ZCs. The transcription factor XBP1 binds the Mist1promoter and induces its expression in vitro and expands the ER in other cell types. We investigated whether XBP1 activates Mist1 to regulate ZC differentiation.
METHODS:
: Xbp1 was inducibly deleted in mice using a tamoxifen/Cre-loxP system; effects on ZC size and structure (ER and granule formation) and gastric differentiation were studied and quantified for up to 13 months after deletion using morphologic, immunofluorescence, quantitative reverse-transcriptase PCR, and immunoblot analyses. Interactions between XBP1 and the Mist1 promoter were studied by chromatin immunoprecipitation from mouse stomach and in XBP1-transfected gastric cell lines.
RESULTS:
: Tamoxifen-induced deletion of Xbp1 ( Xbp1Delta) did not affect survival of ZCs but prevented formation of their structure. Xbp1DeltaZCs shrank 4-fold, compared to those of wild-type mice, with granulogenesis and cell shape abnormalities and disrupted rER. XBP1 was required and sufficient for transcriptional activation of MIST1. Despite severe structural defects, ZCs that developed in the absence of XBP1 expressed ZC markers (intrinsic factor, pepsinogen C) but did not lose expression of progenitor NC markers.
CONCLUSIONS:
: XBP1 controls the transcriptional regulation of ZC structural development; it expands the lamellar rough ER and induces MIST1expression to regulate formation of large granules. XBP1 is also required for loss of mucous NC markers as ZCs form.

Affiliation

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110.

Journal Details

This article was published in the following journal.

Name: Gastroenterology
ISSN: 1528-0012
Pages:

Links

PubMed Articles [22759 Associated PubMed Articles listed on BioPortfolio]

The transcription factor XBP1 is selectively required for eosinophil differentiation.

The transcription factor XBP1 has been linked to the development of highly secretory tissues such as plasma cells and Paneth cells, yet its function in granulocyte maturation has remained unknown. Her...

ER Stress in Dendritic Cells Promotes Cancer.

XBP1 is part of the ER stress response, and when activated in cancer cells, it fosters tumor growth. In this issue of Cell, Cubillos-Ruiz et al. demonstrate that XBP1 in tumor-infiltrating dendritic ...

Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity.

The HSP40 cochaperone SEC63 is associated with the SEC61 translocon complex in the ER. Mutations in the gene encoding SEC63 cause polycystic liver disease in humans; however, it is not clear how alter...

Differential induction of plasma cells by isoforms of human TACI.

Subjects with common variable immune deficiency (CVID) may have mutations in trans-membrane activator calcium modulator and cyclophylin ligand interactor (TACI). Unlike the murine gene, human TACI und...

Evidence of the activation of unfolded protein response in granulosa and cumulus cells during follicular growth and maturation.

The objective of the present study is to investigate whether unfolded protein response (UPR), activated by endoplasmic reticulum (ER) stress, in granulosa cells (GC) and cumulus cells (CC) is involved...

Clinical Trials [5976 Associated Clinical Trials listed on BioPortfolio]

A Study Using Recombinant Human Chorionic Gonadotrophin (rhCG, Ovidrel®) in the Induction of Final Follicle Maturation and Early Luteinization in Chinese Women Undergoing in Vitro Fertilization and Embryo Transfer (IVF/ET)

This was an open, randomized, comparative study using rhCG (Ovidrel) in the induction of final follicle maturation and early luteinization in Chinese female subjects undergoing IVF or ET.

S-1, Cisplatin-based Chemoradiotherapy, Induction Chemotherapy, Locally Advanced Gastric Adenocarcinoma

Currently, for further improved survival outcome, new cytotoxic compounds such as irinotecan and docetaxel have been combined with 5-FU/cisplatin. However, triplet regimen often burdened w...

Insulin Food Supplement for Preterm Infants

GENERAL:The study will evaluate the effect of insulin food supplement on preterm infants, born between 26-33 weeks of pregnancy, weighing over 750 grams, who meet the inclusion and exclusi...

Screening for Gastric Cancer in High-Risk Population

Introduction: Gastric cancer is the world's second largest cause of cancer related deaths. In the Western world, as well as in Israel, this malignancy is less prevalent than colorectal can...

Monitoring Natural Killer Cells in Multiple Sclerosis Patients Treated With Fingolimod

Data on fingolimod effects on NK cells are so far conflicting. A longitudinal study on fingolimod treated kidney transplant patients showed that NK cells were not influenced in any of the ...

Medical and Biotech [MESH] Definitions

Rounded or pyramidal cells of the GASTRIC GLANDS. They secrete HYDROCHLORIC ACID and produce gastric intrinsic factor, a glycoprotein that binds VITAMIN B12.

Neuroendocrine cells in the glands of the GASTRIC MUCOSA. They produce HISTAMINE and peptides such as CHROMOGRANINS. ECL cells respond to GASTRIN by releasing histamine which acts as a paracrine stimulator of the release of HYDROCHLORIC ACID from the GASTRIC PARIETAL CELLS.

Vagal denervation of that part of the STOMACH lined with acid-secreting mucosa (GASTRIC MUCOSA) containing the GASTRIC PARIETAL CELLS. Since the procedure leaves the vagal branches to the antrum and PYLORUS intact, it circumvents gastric drainage required with truncal vagotomy techniques.

Epithelial cells that line the basal half of the GASTRIC GLANDS. Chief cells synthesize and export an inactive enzyme PEPSINOGEN which is converted into the highly proteolytic enzyme PEPSIN in the acid environment of the STOMACH.

A subtype of cholecystokinin receptor found primarily in the CENTRAL NERVOUS SYSTEM and the GASTRIC MUCOSA. It may play a role as a neuromodulator of dopaminergic neurotransmission the regulation of GASTRIC ACID secretion from GASTRIC PARIETAL CELLS.


Advertisement
 

Relevant Topic

Enzymes
Latest News Clinical Trials Research Drugs Reports Corporate
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...

Advertisement
 

Searches Linking to this Article