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Peer-reviewedCC BY-NC-NDnpj Regenerative Medicine

Food-derived peptide RDP3 mitigates pyroptosis to enhance oral mucosal repair via the IL-2Rβ/PI3K axis

  • Junyuan Wang1
  • Yuliu Yang2
  • Zeqiong Ru2
  • Yingyu Zhang2
  • Xueying Xiong2
  • Yujing Ding1
  • Xin Yu1
  • Mengfan Ma1
  • Wenrou Su3
  • Yihang Huang2
  • Xinwang Yang4
  • Naixin Liu5
1 more authors
  • Ying Wang6
6 affiliations
  1. 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
  2. 2Key Laboratory of Skin and Mucosal Injury Repair, Regeneration & Active Peptides of Yunnan Provincial Department of Education, Regenerative Medicine Research Center, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China
  3. 3Yunnan Characteristic Plant Extraction Laboratory Co. Ltd., Kunming, Yunnan, China
  4. 4Key Laboratory of Skin and Mucosal Injury Repair, Regeneration & Active Peptides of Yunnan Provincial Department of Education, Regenerative Medicine Research Center, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China. [email protected]
  5. 5Key Laboratory of Skin and Mucosal Injury Repair, Regeneration & Active Peptides of Yunnan Provincial Department of Education, Regenerative Medicine Research Center, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China. [email protected]
  6. 6Key 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. [email protected]
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{wang2026foodderived,
  title = {{Food-derived peptide RDP3 mitigates pyroptosis to enhance oral mucosal repair via the IL-2Rβ/PI3K axis}},
  author = {Junyuan Wang and Yuliu Yang and Zeqiong Ru and Yingyu Zhang and Xueying Xiong and Yujing Ding and Xin Yu and Mengfan Ma and Wenrou Su and Yihang Huang and Xinwang Yang and Naixin Liu and Ying Wang},
  journal = {npj Regenerative Medicine},
  year = {2026},
  month = jun,
  doi = {10.1038/s41536-026-00487-6},
  url = {https://doi.org/10.1038/s41536-026-00487-6},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Food-derived peptide RDP3 mitigates pyroptosis to enhance oral mucosal repair via the IL-2Rβ/PI3K axis
AU  - Junyuan Wang
AU  - Yuliu Yang
AU  - Zeqiong Ru
AU  - Yingyu Zhang
AU  - Xueying Xiong
AU  - Yujing Ding
AU  - Xin Yu
AU  - Mengfan Ma
AU  - Wenrou Su
AU  - Yihang Huang
AU  - Xinwang Yang
AU  - Naixin Liu
AU  - Ying Wang
PY  - 2026
DA  - 2026/06/20
JO  - npj Regenerative Medicine
DO  - 10.1038/s41536-026-00487-6
UR  - https://doi.org/10.1038/s41536-026-00487-6
AB  - 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.
SN  - 2057-3995
ER  -