XBP1 controls maturation of gastric zymogenic cells by induction of MIST1 and expansion of the rough endoplasmic reticulum.
Summary of "XBP1 controls maturation of gastric zymogenic cells by induction of MIST1 and expansion of the rough endoplasmic reticulum."
: 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.
: 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.
: 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.
: 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.
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.
This article was published in the following journal.
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20816838
- DOI: http://dx.doi.org/10.1053/j.gastro.2010.08.050
Breast cancer is highly metastatic disease and the most lethal of the gynecologic malignancies. Epithelial-to-mesenchymal is a crucial process for the invasion of epithelial tumors. Recent studies rev...
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...
The X-box binding protein 1 (XBP1) is not only an important component of the unfolded protein response (UPR), but also an important nuclear transcription factor. Upon endoplasmic reticulum stress, XBP...
Gastric cancer cell are not particularly sensitive to Ara-C, a deoxycytidine analog that affects DNA synthesis. In the present study, AGS and MKN-45 gastric cancer cell lines were treated with Ara-C t...
Human γδ T cells expressing the Vγ9Vδ2 T cell receptor can induce maturation of dendritic cells (DC) into antigen-presenting cells (APC) and B cells into antibody-secreting plasma cells. Since B c...
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.
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...
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...
Developmental dyslexia is a frequent learning disability. The aim of this study is to compare auditory evoked cortical responses to syllables and tones in developmental dyslexia and contro...
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.