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Food-derived peptide RDP3 mitigates pyroptosis to enhance oral mucosal repair via the IL-2Rβ/PI3K axis
Junyuan Wang1, Yuliu Yang2, Zeqiong Ru2
1Key Laboratory of Chemistry in Ethnic Medicinal Resources & Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming, Yunnan, China.
None:
Oral ulcers represent a prevalent mucosal disease with incompletely elucidated pathogenesis and a clinical deficiency in multifunctional therapeutics. This study investigates a food-derived peptide, RDP3, with tissue-penetrating capability, which significantly promotes repair of oral ulcer mucosal in vivo and in vitro in a low concentration (1 nM). This is the first time to report a food-origin peptide capable of accelerating oral ulcer mucosal repair. RDP3 can not only accelerate wound healing but also restore microbiome homeostasis. Mechanistically, RDP3 functions as a novel peptide-antagonist of the interleukin-2 receptor β subunit (IL-2Rβ; binding affinity KD = 0.99 μM). This interaction suppresses pathological PI3K signaling, thereby inhibiting NLRP3/GSDMD-mediated pyroptosis, reducing inflammation, and promoting mucosal regeneration. These findings position RDP3 as a promising multifunctional therapeutic candidate for oral ulcer treatment.