Nononcogenic restoration of the intestinal barrier by E. coli-delivered human EGF

Although mucoactive proteins, such as epidermal growth factor (EGF), could improve clinical outcomes of intestinal ulcerative diseases, their gastrointestinal application is limited because of their proteolytic digestion or concerns about tumor promotion. In the present study, ATP-binding cassette (ABC) transporter-linked secretion of human EGF from probiotic Escherichia coli (EGF-EcN) was created to promote beneficial actions of the EGF receptor, which is notably attenuated in patients with intestinal ulcerative injuries. Preventive and postinjury treatment with EGF-EcN alleviated intestinal ulcers and other readouts of disease severity in murine intestinal ulcer models. EGF-EcN administration promoted the restitutive recovery of damaged epithelial layers, particularly via upward expansion of highly proliferating progenitor cells from the lower crypts. Along with the epithelial barrier benefit, EGF-EcN improved goblet cell-associated mucosal integrity, which controls the access of luminal microbiota to the underlying host tissues. Despite concern about the oncogenic action of EGF, EGF-EcN did not aggravate colitis-associated colon cancer; instead, it alleviated protumorigenic activities and improved barrier integrity in the lesions. All findings indicate that probiotic bacteria-based precision delivery of human EGF is a promising mucosal intervention against gastrointestinal ulcers and malignant distress through crypt-derived barrier restoration.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:4

Enthalten in:

JCI insight - 4(2019), 16 vom: 22. Aug.

Sprache:

Englisch

Beteiligte Personen:

Yu, Mira [VerfasserIn]
Kim, Juil [VerfasserIn]
Ahn, Jung Hoon [VerfasserIn]
Moon, Yuseok [VerfasserIn]

Links:

Volltext

Themen:

62229-50-9
ATP-Binding Cassette Transporters
Epidermal Growth Factor
Growth factors
Inflammatory bowel disease
Journal Article
Microbiology
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 17.09.2020

Date Revised 17.09.2020

published: Electronic

Citation Status MEDLINE

doi:

10.1172/jci.insight.125166

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM300446497