A Bivalent Aptamer-Based DNA Agonist for EGFR Signaling Effectively Alleviates Ulcerative Colitis In Vivo.
ACS Chem Biol
; 19(6): 1280-1290, 2024 Jun 21.
Article
in En
| MEDLINE
| ID: mdl-38837175
ABSTRACT
While epidermal growth factor (EGF) shows promise in addressing the clinical manifestations of intestinal ulcerative diseases by activating the EGF receptor (EGFR)-mediated cell signaling, its clinical application is hampered by poor protein hydrolytic stability, low thermostability, and difficulty in modification. The development of a novel EGFR agonist for ulcerative colitis remains an urgent need, necessitating innovative solutions to overcome the limitations of current therapies via recombinant EGF protein. Herein, we introduce a novel DNA agonist for EGFR, Dimer-YL, which employs a bivalent aptamer to induce stable receptor dimerization, thereby activating the EGFR signaling and related cell behaviors. Dimer-YL has been demonstrated to recapitulate the EGF-promoted cellular behaviors, including proliferation and migration, as well as repair the damage of intercellular tight junctions. Furthermore, our findings demonstrate the potent therapeutic function of Dimer-YL in alleviating DSS-induced ulcerative colitis in vivo. Together, the present work has revealed Dimer-YL as an innovative DNA molecule for effective EGFR activation, offering promise for the development of EGFR-agonistic agents for therapeutic purposes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Colitis, Ulcerative
/
Aptamers, Nucleotide
/
ErbB Receptors
Limits:
Animals
/
Humans
Language:
En
Journal:
ACS Chem Biol
Year:
2024
Document type:
Article
Country of publication:
United States