Date of Award

4-2018

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Dr. Asma Al Menhali

Second Advisor

Dr. Iltaf Shah

Third Advisor

Dr. Habiba Al Safar

Abstract

The gastric epithelium consists of different types of cells, which are involved in gastric homeostasis by balancing cell proliferation and differentiation. This process involves several signaling molecules such as growth factors, hormones and vitamins. Vitamin D3 (VD3) is engaged in several biological activities. It plays a role in cell differentiation, cell proliferation, immune response and also regulates calcium homeostasis. The biological activities of VD3 are mediated by vitamin D receptor (VDR). Target tissues of VD3 in the gastrointestinal tract were identified earlier in intestine, colon and gastric cancer tissues; however, the normal expression of VDR in stomach is poorly studied. So, the main objectives of this thesis are: 1) to investigate the normal expression, distribution and cellular localization of VDR in gastric epithelium and 2) to study possible role of VDR and VD3 in maintaining gastric stem cells proliferation and differentiation by establishing and analyzing mouse model deficient in VD3. Polymerase chain reaction (PCR) analysis showed that VDR as well as enzymes involved in VD3 metabolism are expressed in the different region of normal mouse stomach. Co-immunostaining analysis showed specific expression of VDR in the acid secreting parietal cells and the different mucus secreting cells. The results suggested that parietal cells and mucous cells are targets for VD3 signaling. To examine the role of VD3 on gastric homeostasis, wild type mice were put on VD3 deficient diet for 3 months. Using Real-Time Polymerase Chain Reaction (Real-Time PCR), stomachs of mice deficient of vitamin D showed significant decrease in expression of parietal cell specific genes (HKα and HKβ) and increase gastrin gene expression. Moreover, quantification for cells in the S-phase of the cell cycle showed significant increase in their number in vitamin D deficient mice compared to controls. Gene expression analysis of VDR signaling genes showed significant decrease in PTHLH, but not other target genes like TRPV6 and p21. This work will add value to the field of stomach biology by providing better understanding of how VD3 and VDR are involved in maintaining gastric epithelial homeostasis and how that is related to some stomach conditions such as low gastric acidity and gastric cancer.

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