Recombinant Adenovirus-Mediated Intestinal Trefoil Factor Gene Therapy for Burn-Induced Intestinal Mucosal Injury

Abstract

Intestinal trefoil factor (ITF) is a small polypeptide with potential medical values whose main pharmacological effects are to alleviate gastrointestinal mucosal injury caused by various injury factors and promote the repair of damaged mucosa. However, its low yield limits its application. The purpose of our study was to construct a recombinant adenoviral vector containing the hITF gene and observe the therapeutic effect of burn-induced intestinal mucosal injury using in vitro and in vivo analysis. First, a recombinant shuttle plasmid was constructed by ligating a pAdTrack-CMV vector with a full-length hITF gene containing a signal peptide and the mature peptide, followed by the recombinant Ad-hITF adenovirus vector after linearization and homologous recombination with the backbone plasmid in the competent BJ5183 strain. Second, the hITF expression level was detected using reverse transcription polymerase chain reaction and western blotting after Ad-hITF infection of colon cancer HT-29 cells. The recombinant adenovirus significantly promoted cell migration in an in vitro wounding model. Finally, we confirmed that the recombinant adenovirus could significantly expedite the healing of intestinal mucosal injury after establishing a mouse model in which severe burns were stimulated and the recombinant adenovirus was delivered by intragastric injection. In summary, we constructed a recombinant adenoviral vector containing the hITF gene and confirmed its role in promoting repair of the intestinal mucosa. Our study provides a novel way to treat burn-induced intestinal mucosal injury.

Effects of stocking density on the growth performance, digestive enzyme activities, antioxidant resistance, and intestinal microflora of blunt snout bream ( Megalobrama amblycephala ) juveniles

“…The intestinal health of the fish in the different groups was different. The secretion of goblet cells can maintain the integrity of the intestinal mucus barrier (Sun et al, ) and relieve symptoms of chronic intestinal inflammation (Nair et al, ). The 30F and 60F groups had more goblet cells than the other groups, reflecting a healthier intestinal state.…”

Intestinal trefoil factor increased the Bcl-2 level in a necrotizingenterocolitis neonate rat model

“…Interestingly, ITF not only promoted cell proliferation and migration, but also special physical function; for example, it helped to stabilize the mucus layer by binding to mucous glycoprotein (14,15). Additionally, experiments have shown that ITF plays an important role in protecting the integrity of the intestinal mucosa and promoting its reconstruction after injury (16)(17)(18)(19). Mice lacking ITF did not heal well after mucosa injury.…”

Chronic rhinosinusitis without nasal polyps is associated with increased expression of trefoil factor family peptides

“…For example, TFF2 delivered intranasally in an allergic mouse model was able to reverse lung remodeling, though it was not able to alter progression of airway inflammation . Likewise, TFF3 delivered orally via an adenoviral vector was able to expedite tissue healing in a mouse model of burn‐induced intestinal mucosal injury, while intraperitoneal injection of TFF3 was able to decrease colonic damage and inflammatory cytokine expression in a mouse model of experimentally‐induced colitis . A small human trial evaluating the efficacy of TFF3 enemas for ulcerative colitis was well‐tolerated but did not show any therapeutic benefit .…”