Effects of orally administered bacteria carrying HIF-1α gene in an experimental model of intestinal ischemia.
OBJECTIVE
Bactofection is delivery of therapeutic genes into target cells using bacteria penetrating the target cell membrane and releasing the gene into the cell. Hypoxia-inducible factor 1α (HIF-1α) represents a potential therapeutic gene to be used for gene delivery in ischemic diseases. The aim of this study was to prove the effects of bacteria-mediated transfer of hypoxia-inducible factor 1α (HIF-1α) in an experimental model of intestinal ischemia in rats.


METHODS
Male Wistar rats with a surgically induced ischemia of colon (cecum) or sham-operated rats were treated by per os application of E. coli carrying therapeutic genes. After 1 week, samples were taken for measurement of oxidative stress markers and expression analyses.


RESULTS
According to our observation, there were no signs or symptoms of ongoing ischemia in gastrointestinal tissue. Interestingly, all experimental groups treated by bacteria, regardless of their ability to invade cells or the presence of HIF-1α gene, showed decreased levels of vascular endothelial growth factor (VEGF) compared to control groups. Similarly, all treatment groups showed increased hematocrit.


CONCLUSIONS
We conclude ineffectiveness of the bacterial gene delivery system. However, the effect of bacteria themselves was obvious. HIF-1 can be activated hypoxia-independently by the action of pathogenic bacteria in the rat intestine. We hypothesize that therapeutic bacterial strain used may compete with siderophore-expressing bacteria present in the gut of rats to force them out and prevent their ability to activate HIF-1 in a hypoxia-independent manner. This phenomenon should be analyzed in detail in further studies.
Gardlik
Roman
R
Institute of Pathophysiology, Comenius University, Bratislava, Slovakia. romangardlik@gmail.com
Hodosy
Julius
J
Palffy
Roland
R
Behuliak
Michal
M
Janega
Pavol
P
Celec
Peter
P
D000284:Administration, Oral; D000818:Animals; D001419:Bacteria / Q000235:genetics*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000628:therapy*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit