14,824 research outputs found
Fibroblast growth factors in gastrointestinal development, homeostasis and injury
Fibroblast growth factors (FGFs) and their receptors (FGFRs) are
essential for controlling cell growth and proliferation, angiogenesis,
wound healing and tumourigenesis. In mammals, there are twenty-three
FGFs and five FGFRs, with each FGFR having different ligand binding
specificities. FGFs are thought to act in a paracrine manner, in which they
are secreted by one cell and activate FGFRs on another cell type, and such
interaction helps to establish the fundamental crosstalk between
epithelium and mesenchyme during development, homeostasis and
tumourigenesis.
This thesis aims to investigate the requirement of FGFR2-isoform IIIb
(Fgfr2b) and one of its ligands, Fgf10, in gastrointestinal (GI)
development, homeostasis and injury, using loss-of-function animal
models. Fgfr2b-/- and Fgf10-/- exhibit similar multi-organ defects,
including intestinal atresia. While caecal and colonic atresia have been
previously described, the mechanism of duodenal atresia and the role of
Fgf signalling in duodenal development have not been fully established.
We demonstrate that absence of Fgfr2b or Fgf10 leads to decreased tissue
proliferation and increased apoptosis in the duodenum, contributing to
duodenal atresia. These mutants also develop gastric heterotopia in the
rostral duodenum due to loss of gastric-intestinal boundary specification.
In addition, we demonstrate reduced expression of Wnt targets Tcf1 and
Tcf4 in the small intestine, with corresponding downregulation of Lgr5, an
intestinal stem cell marker, and Cdx1, a homeobox gene involved in
anterior-posterior patterning. We show by in vitro that Fgf10-Fgfr2b
signalling is able to regulate Tcf4 expression via the Grb2/Sos/Ras/MAPK
pathway.
In order to study the requirement of Fgfr2b in intestinal homeostasis and
injury, we crossed a transgenic line bearing a progesterone antagonist
(RU486)-dependent Cre recombinase (A33-CrePR) expressed under the
control of the intestinal-specific A33 antigen promoter, with an existing
conditional Fgfr2b line. Following RU486 administration with/without
administration of dextran sodium sulphate (DSS) thereafter to induce
ulcerative colitis (UC), the A33-CrePR+/Fgfr2bflox/flox targeted Fgfr2b
ablation with high efficiency across the small and large intestine. We
demonstrate that significant downregulation of Fgfr2b does not affect
intestinal homeostasis, but significantly increases the susceptibility of
colonic epithelium to UC and delays wound healing, contributed by
reduced epithelial proliferation.
In order to study the requirement of Fgfr2b in gastric homeostasis, we
characterised two stomach-specific minimal promoters for trefoil factor 1
(Tff1) and H+K+-ATPase (Atp4b) to generate two inducible Cre
recombinase (CreERT2) lines. Gastric surface mucous cells and acidproducing
parietal cells express Tff1 and Atp4b respectively, as well as
Fgfr2b. We demonstrate by in vitro that Atp4b nucleotide -1,035bp to +24
bp and Tff1 nucleotide -641 bp to +28 bp are optimal for driving Cre
expression in the mouse stomach.
Thus, our novel data provides evidence that Fgfr2b and Fgf10 are required
for normal duodenal morphogenesis and differentiation, and Fgfr2b
confers protection against DSS-induced colonic injury and promotes
wound repair
Intergenerational Brand Transfer on Cosmetics Products
The study examined intergenerational brand transfer from mother to daughter for cosmetics products using evolutionary psychology as the framework. Data were collected from 30 participants (14 mothers, 16 daughters) using in-depth semi-structured interviews. The results showed a strong intergenerational transfer of brand loyalty. Most of the daughters used either the full range (25%) or a part of the range (50%) of cosmetics products used by their mothers. A majority (87.5%) of the daughters reported that they knew the cosmetics brands used by their mothers, and the interviews with their mothers showed that 75% of them accurately remembered the brands. The mothers’ influence was achieved through brand visibility, daughters’ trial use of the cosmetics, and the mothers acting as product suppliers. Price and product characteristics ranked the highest among the daughters’ and mothers’ considerations in purchasing cosmetics, showing that the daughters had adopted their mothers’ behavior and thinking in product selection. The extended family also influenced the daughters’ choice of cosmetics brands because of the close-knit community
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