Regulation of
Intestinal Nutrient Transporters
My laboratory is interested in developmental, nutritional,
gastrointestinal and environmental regulation of gene expression.
We chose the rat small intestine as model because it provides an
excellent example of how developmental timing mechanisms are exquisitely
programmed to match changes in function. During birth, placental
nutrition ceases and enteral nutrition begins. The small intestine
acquires many enzymes and transporters before birth to digest then
absorb nutrients from milk. During weaning, the small intestine
synthesizes different types or different numbers of enzymes and
transporters to match expected changes in luminal substrate concentrations
arising from an increasing variety of food. We are interested in
identifying the signals that lead to adaptive changes in transporter
expression. We use microarray hybridization to determine the pathways
of substrate:transporter signal transduction. Once a candidate signaling
molecule is identified, it is then stimulated or inhibited to determine
its role in regulating transporter gene expression during development.
This project is relevant to premature babies born with underdeveloped
intestines: if late onset transporters can be induced to appear
earlier during development, it would allow feeding of critical nutrients
that would otherwise cause complications in the developing intestine.
Conventional indicators of malnutrition are clinical: excessive
changes in body weight and abnormal plasma profiles of nutrients
are among many. High throughput genetic screening methods now allow
investigators to identify factors that change acutely in response
to malnutrition, well before more serious symptoms are detected.
We are using a fish model and the techniques of microarray, subtractive
hybridization and RT-PCR to identify genes whose mRNA abundance
changes markedly in response to dietary restriction or excess of
a nutrient. The validity of these potential predictors of malnutrition
is compared with that of conventional indicators. Their importance
is evaluated by altering their function using pharmacological agents,
to determine how alterations of their expression lead to clinical
symptoms.
In situ hybridization sections of intestinal mucosa showing villi
from rat pups fed high (left panel) or low (right) fructose feeds.
Mucosa of rats fed high fructose contains high levels of fructose
transporter mRNA.
• Jiang, L. and R. P. Ferraris (2001) Developmental
reprogramming of rat GLUT5 requires de novo mRNA and protein synthesis.
Am. J. Physiol. 280:G113-G120.
• Ferraris, R. P. (2001) Dietary and developmental regulation
of intestinal sugar transport. Biochem. J. 360:276-295.
• Cui, X., L. Jiang and R.P. Ferraris (2003) Regulation
of rat intestinal GLUT2 mRNA abundance by luminal and systemic factors.
Biochim. Biophys. Acta (Biomembranes) 1612:178-185.
• Sugiura, S.H., N.K. McDaniel and R.P. Ferraris. In
vivo fractional phosphorus absorption and NaPi-II mRNA expression
in rainbow trout are upregulated by dietary P restriction. Am J
Physiol Regulatory Integrative Comp Physiol, Jun 2003; 10.1152/ajpregu.00127.2003
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