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
  • 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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