The Frog Skin-Derived Antimicrobial Peptide Suppresses Atherosclerosis by Modulating the KLF12/p300 Axis Through miR-590-5p
Year: 2025
Type: article
Abstract: Inflammation is a hallmark of atherosclerosis (AS), a complex chronic vascular disease. This study investigates the anti-atherosclerotic effects of the frog skin antimicrobial peptide(AMP) C-1b(3-13) in vitro and in vivo, focusing on the anti-inflammatory mechanism mediated by the miR-590-5p/KLF12/p300 axis in ox-LDL-induced PMA-THP-1 foam cells. MicroRNA(miRNA) sequencing was used to investigate the effects of AMP C-1b(3-13) on miRNA expression in ox-LDL-induced foam cells. Pro-inflammatory cytokine secretion regulated by miR-590-5p was detected by ELISA. Potential targets of miR-590-5p were bioinformatically predicted and validated through dual-luciferase reporter and RNA Immunoprecipitation(RIP)-qPCR assays. Western blot was used to assess the effects of C-1b(3-13) on Krüppel-like factor 12(KLF12), nuclear p300, and nuclear factor kappa B(NF-κB) pathway proteins; ApoE−/− mice were utilized to establish the AS mouse model. Oil Red O (ORO) and hematoxylin and eosin (H&E) staining detected plaque formation and morphological changes in the aortic root. Immunohistochemistry analyzed CD68+(M1) and CD206+(M2) macrophage distribution within arterial plaques. miR-590-5p significantly suppressed pro-inflammatory cytokine secretion in ox-LDL-induced foam cells. Mechanistically, miR-590-5p directly targeted the 3′-untranslated region of KLF12 mRNA, inhibiting KLF12 expression, reducing nuclear p300 accumulation, and subsequently attenuating NF-κB signaling pathway activation. Furthermore, AMP C-1b(3-13) treatment effectively attenuated inflammatory responses by upregulating miR-590-5p, which downregulated KLF12 expression, diminished nuclear p300 levels, and inhibited NF-κB signaling. In ApoE−/− AS mice, C-1b(3-13) treatment markedly reduced aortic plaque formation, improved lipid metabolism, and suppressed inflammatory responses through the same signaling axis. These findings reveal a novel miR-590-5p-mediated regulatory mechanism in AS and identify AMP C-1b(3-13) as a promising therapeutic agent targeting miR-590-5p/KLF12/p300/NF-κB pathway.
Authors: Fan Fan, Meng-Miao Li, Zhong-Peng Qiu, Zhen-Jia Li, De-Jing Shang
Institution: Liaoning Normal University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W4416746674