Plant miRNA osa-miR172d-5p suppressed lung fibrosis by targeting Tab1

Abstract

Lung fibrosis, including idiopathic pulmonary fibrosis, is an intractable disease accompanied by an irreversible dysfunction in the respiratory system. Its pathogenesis involves the transforming growth factorβ (TGFβ)-induced overproduction of the extracellular matrix from fibroblasts; however, limited countermeasures have been established. In this study, we identified osa-miR172d-5p, a plant-derived microRNA (miR), as a potent anti-fibrotic miR. In silico analysis followed by an in vitro assay based on human lung fibroblasts demonstrated that osa-miR172d-5p suppressed the gene expression of TGF-β activated kinase 1 (MAP3K7) binding protein 1 (Tab1). It also suppressed the TGFβ-induced fibrotic gene expression in human lung fibroblasts. To assess the anti-fibrotic effect of osa-miR172d-5p, we established bleomycin-induced lung fibrosis models to demonstrate that osa-miR172d-5p ameliorated lung fibrosis. Moreover, it suppressed Tab1 expression in the lung tissues of bleomycin-treated mice. In conclusion, osa-miR172d-5p could be a potent candidate for the treatment of lung fibrosis, including idiopathic pulmonary fibrosis.

Atypical Plant miRNA cal-miR2911: Robust Stability against Food Digestion and Specific Promoting Effect on Bifidobacterium in Mice

“…The early investigation on miR2911 reported its antiviral potential against influenza A virus . After that, several studies showed that miR2911 was able to inhibit tumor growth and lung fibrosis in a cross-kingdom manner. − We here proved for the first time that miR2911 could modulate the growth of gut microbes in vivo , which is an extension of the cross-kingdom effect of exogenous miRNAs, indicating the existence of direct interactions between dietary miRNAs and gut microbes. miR2911 can get into cells of B.…”

Evidence of Cross-Kingdom Gene Regulation by Plant MicroRNAs and Possible Reasons for Inconsistencies

“…The current evidence indicates that plant miRNAs that exert cross-kingdom gene regulation obey the principles of miRNA−target recognition in animals. 16,33,35,63 The results of the present study support the emerging idea that a novel gene therapy strategy based on plant miRNAs may be feasible. 82,83 However, because plant miRNAs are nascent active elements in plants, much remains to be explored regarding their pharmacology and medicinal use.…”

“…For example, which principle does a plant miRNA functioning in animals obey? The current evidence indicates that plant miRNAs that exert cross-kingdom gene regulation obey the principles of miRNA–target recognition in animals. ,,, …”

“…The present study suggests that a reliable plant miRNA candidate can potentially achieve cross-kingdom gene regulation, with all delivery mechanisms listed in Tables –. However, the best delivery mechanism is difficult to determine based on the available evidence; ,,,,− ,,− specifically, few studies have compared the advantages and disadvantages of these methods, and only one study found that herbal decoction-borne plant miRNAs are more effective at inhibiting HBsAg expression than comparable synthetic plant miRNAs mimics in mice via oral delivery . The selection of the best delivery mechanism is complicated.…”

“…Over the past decade, a significant amount of research has focused on validating this cross-species gene regulation phenomenon, but a consensus has not yet been reached. , This study aims to determine whether cross-species gene regulation by orally consumed plant miRNAs can indeed occur. The study classified plant miRNAs into various categories, including miRNAs carried by extracellular vesicle (EV), − extracted plant miRNAs, − miRNAs borne by herbal decoctions, ,,,, synthetic plant miRNAs mimics, ,,,,,,− and miRNAs present in plant tissues/juices ,,,,,,− (Figure ). For each category of plant miRNAs, we systematically collected and reviewed the evidence for cross-species gene regulation.…”