2. Academic Validation
  3. miR-186-5p targets TGFβR2 to inhibit RAW264.7 cell migration and proliferation during mouse skin wound healing

miR-186-5p targets TGFβR2 to inhibit RAW264.7 cell migration and proliferation during mouse skin wound healing

  • Environ Toxicol. 2023 Aug 11. doi: 10.1002/tox.23914.
Yinglei Wang 1,  Yuansheng Li 1,  Dan Ni 1,  Ziqi Wei 1,  Zhe Fu 1,  Chao Li 1,  Huiling Sun 1,  Yutong Wu 1,  Yilin Li 1,  Yingxuan Zhang 1,  Naixin Liu 1,  Yixiang Liu 2,  Zhuo Wang 2,  Jiayi Li 1,  Dandan Sun 1,  Li He 3,  Ying Yang 4,  Ying Wang 2,  Xinwang Yang 1
Affiliations

Affiliations

  • 1 Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China.
  • 2 Key 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, China.
  • 3 Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, China.
  • 4 Department of Endocrinology, Affiliated Hospital of Yunnan University, Kunming, China.
PMID: 37565786 DOI: 10.1002/tox.23914
Abstract

Background: Active Peptides play a vital role in the development of new drugs and the identification and discovery of drug targets. As the first reported native peptide homodimer with pro-regenerative potency, OA-GP11d could potentially be used as a novel molecular probe to help elucidate the molecular mechanism of skin wound repair and provide new drug targets.

Methods: Bioinformatics analysis and luciferase assay were adopted to determine MicroRNAs (miRNAs) and its target. The prohealing potency of the miRNA was determined by MTS and a Transwell experiment against mouse macrophages. Enzyme-linked immunosorbent assay, realtime polymerase chain reaction, and western blotting were performed to explore the molecular mechanisms.

Results: In this study, OA-GP11d was shown to induce Mus musculus microRNA-186-5p (mmu-miR-186-5p) down-regulation. Results showed that miR-186-5p had a negative effect on macrophage migration and proliferation as well as a targeted and negative effect on TGF-β type II receptor (TGFβR2) expression and an inhibitory effect on activation of the downstream Smad Family member 2 (SMAD2) and protein-p38 kinase signaling pathways. Importantly, delivery of a miR-186-5p mimic delayed skin wound healing in mice.

Conclusion: miR-186-5p regulated macrophage migration and proliferation to delay wound healing through the TGFβR2/SMAD2/p38 molecular axes, thus providing a promising new pro-repair drug target.

Keywords

OA-GP11d; TGFβR2; miR-186-5p; pro-healing peptide; wound healing.

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