Delivery of MiRNA-92a Inhibitor Using RP1-Linked Peptide Elicits Anti-Inflammatory Effects in an Acute Lung Injury Model
- Authors
- Zhuang, Chuanyu; Piao, Chunxian; Choi, Myoungjee; Ha, Junkyu; Lee, Minhyung
- Issue Date
- Jul-2021
- Publisher
- AMER SCIENTIFIC PUBLISHERS
- Keywords
- Acute Lung Injury; RP1; Delivery; Inflammation; MicroRNA-92a
- Citation
- Journal of Biomedical Nanotechnology, v.17, no.7, pp.1273 - 1283
- Indexed
- SCIE
SCOPUS
- Journal Title
- Journal of Biomedical Nanotechnology
- Volume
- 17
- Number
- 7
- Start Page
- 1273
- End Page
- 1283
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/141497
- DOI
- 10.1166/jbn.2021.3102
- ISSN
- 1550-7033
- Abstract
- Acute lung injury (ALI) is an inflammatory lung disease. miRNA-92a (miR92a) is induced in the lungs of ALI patients and mediates inflammatory reactions. In this study, a RP1-linked R3V6 (RP1R3V6) peptide was synthesized and evaluated as a carrier of anti-microRNA-92a oligonucleotide (AMO92a) into the lungs of an ALI animal model. In addition to the carrier function, the RP1-linked peptide can have anti-inflammatory effects in the lungs, since RP1 is an antagonist of the receptors for advanced glycation end-products (RAGEs). In a gel retardation assay, the RP1R3V6 peptide formed a spherical complex with AMO92a. In an in vitro delivery assay to L2 rat lung epithelial cells, RP1R3V6 had a lower AMO92a delivery efficiency than R3V6 and polyethyleneimine (PEI25k; 25 kDa). However, RP1R3V6 had an additional anti-inflammatory effect, reducing tumor necrosis factor-alpha (TNF-alpha) in lipopolysaccharide-activated macrophage cells. With the combined effects of AMO92a and RP1, the RP1R3V6/AM092a complex reduced the miR92a level more efficiently than did the R3V6/AMO92a and PEI25k/AMO92a complexes. The RP1R3V6/AM092a complex was administered into the lungs of ALI animals by intratracheal instillation. As a result, the expression of phosphatase and tensin homolog, a target of miR92a, was increased in the lungs. Furthermore, the RP1R3V6/AM092a complex decreased the TNF-alpha and interleukin-1 beta (IL-1 beta) levels more efficiently than did the PEI25k/AMO92a and R3V6/AMO92a complexes, decreasing the damage in the lungs. These results suggest that RP1R3V6 is a useful carrier of AMO92a and has anti-inflammatory effects in an ALI animal model.
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