Pre-administration of PepFect6-microRNA-146a nanocomplexes inhibits inflammatory responses in keratinocytes and in a mouse model of irritant contact dermatitis

Urgard, Egon; Lorents, Annely; Klaas, Mariliis; Padari, Kärt; Viil, Janeli; Runnel, Toomas; Langel, Kent; Kingo, Külli; Tkaczyk, Eric R.; Langel, Ülo; Maimets, Toivo; Jaks, Viljar; Pooga, Margus; Rebane, Ana

doi:10.1016/j.jconrel.2016.06.006

Cited by 43 publications

(40 citation statements)

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“…In addition, our results are in line with recently published in vivo mouse studies (Srivastava et al , 2016; Urgard et al , 2016) suggesting that overexpression or local administration of miR-146a/b mimics may have potential for the treatment of psoriasis.…”

Section: Discussionsupporting

confidence: 91%

“…Accordingly, 146a−/− mice developed more severe disease in mouse models of AD and psoriasis, while pre-injection of miR-146a alleviated the inflammation in mouse models of irritant contact dermatitis and psoriasis (Rebane et al , 2014; Srivastava et al , 2016; Urgard et al , 2016). As miR-146a/b have similar expression level in vivo in human and mouse skin, miR-146a/b together might have remarkably stronger influence than studies performed with miR-146a−/− mice demonstrate.…”

Section: Discussionmentioning

confidence: 99%

“…In human primary keratinocytes, miR-146a inhibits the expression of many pro-inflammatory factors, including CCL5 and IL-8 (Meisgen et al , 2014; Rebane et al , 2014). miR-146a has been shown to act as anti-inflammatory miRNA in mouse models of AD (Rebane et al , 2014), irritant contact dermatitis (Urgard et al , 2016) and psoriasis (Srivastava et al , 2016). The single nucleotide polymorphism (SNP) rs2910164 located in miR-146a precursor has been suggested to be associated with psoriasis in Han Chinese population (Zhang et al , 2014) and among Caucasians (Srivastava et al , 2016).…”

Section: Introductionmentioning

confidence: 99%

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miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis

Hermann

Runnel

Aab

et al. 2017

Journal of Investigative Dermatology

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miR-146a inhibits inflammatory responses in human keratinocytes and in different mouse models of skin inflammation. Little is known about the role of miR-146b in the skin. In the present study, we confirmed the increased expression of miR-146a and miR-146b (miR-146a/b) in lesional skin of psoriasis patients. The expression of miR-146a was about 2-fold higher than that of miR-146b in healthy human skin and it was more strongly induced by stimulation of pro-inflammatory cytokines in keratinocytes and fibroblasts. miR-146a/b target genes regulating inflammatory responses or proliferation were altered in the skin of psoriasis patients, among which FERMT1 was verified as direct target of miR-146a. In silico analysis of genome-wide data from >4,000 psoriasis cases and >8,000 controls confirmed a moderate association between psoriasis and genetic variants in miR-146a gene. Transfection of miR-146a/b suppressed and inhibition enhanced keratinocyte proliferation and the expression of psoriasis-related target genes. Enhanced expression of miR-146a/b-influenced genes was detected in cultured keratinocytes from miR-146a−/− and skin fibroblasts from miR-146a−/− and miR-146b−/− mice stimulated with psoriasis-associated cytokines as compared to wild type mice. Our results indicate that besides miR-146a, miR-146b is expressed and might be capable of modulation of inflammatory responses and keratinocyte proliferation in psoriatic skin.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis

Hermann

Runnel

Aab

et al. 2017

Journal of Investigative Dermatology

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“…We could hypothesize that RICK:siRNA nanoparticles were formed in the same manner: first the formation of ~20 nm spheres composed of RICK:siRNA (R = 20) which self-associate in a “beads necklace”-like manner to nanoparticles of ~100 nm. Such assembly could be also compared to the “large branching agglomerates” described for the parental peptide CADY in the presence of miRNA [50]. …”

Section: Resultsmentioning

confidence: 99%

A retro-inverso cell-penetrating peptide for siRNA delivery

et al. 2017

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BackgroundSmall interfering RNAs (siRNAs) are powerful tools to control gene expression. However, due to their poor cellular permeability and stability, their therapeutic development requires a specific delivery system. Among them, cell-penetrating peptides (CPP) have been shown to transfer efficiently siRNA inside the cells. Recently we developed amphipathic peptides able to self-assemble with siRNAs as peptide-based nanoparticles and to transfect them into cells. However, despite the great potential of these drug delivery systems, most of them display a low resistance to proteases.ResultsHere, we report the development and characterization of a new CPP named RICK corresponding to the retro-inverso form of the CADY-K peptide. We show that RICK conserves the main biophysical features of its L-parental homologue and keeps the ability to associate with siRNA in stable peptide-based nanoparticles. Moreover the RICK:siRNA self-assembly prevents siRNA degradation and induces inhibition of gene expression.ConclusionsThis new approach consists in a promising strategy for future in vivo application, especially for targeted anticancer treatment (e.g. knock-down of cell cycle proteins).Graphical abstractRICK-based nanoparticles: RICK peptides and siRNA self-assemble in peptide-based nanoparticles to penetrate into the cells and to induce target protein knock-down. Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-017-0269-2) contains supplementary material, which is available to authorized users.

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“…The ear oedema essay was performed according to a previously reported method [27,28] with slight modifications in Kunming mice. After a 1-h pre-treatment, 20 lL DMB was topically applied on the right ear (10 lL each on the anterior and posterior surfaces).…”

Section: Anti-inflammatory Effects Of Msc-cdsmentioning

confidence: 99%

Novel mulberry silkworm cocoon-derived carbon dots and their anti-inflammatory properties

Wang

Zhang

Kong

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Mulberry silkworm cocoon (MSC) carbonisata has been used for the treatment of inflammatory diseases for hundreds of years; however, after years of research efforts, little information is available on its antiinflammatory components and underlying mechanism. We developed novel carbon dots (CDs) derived from MSC carbonisata (MSC-CDs), for the first time, with an average diameter of 2.26-9.35 nm and a quantum yield (QY) of 6.32%. The MSC-CDs were prepared using a modified pyrolysis method, and no further modification and external surface passivation agent was required. With abundant surface groups, MSC-CDs showed distinct solubility and bioactivity. In this study, we innovatively used three classical experimental models of inflammation to evaluate the anti-inflammatory bioactivity of MSC-CDs. The results indicated that MSC-CDs exhibited marked anti-inflammatory bioactivity which was likely mediated by inhibition of the expression of interleukin-6 and tumour necrosis factor-a. These results suggest that MSC-CDs possess a remarkable anti-inflammatory property, which provides evidence to support further investigation of the considerable potential and effective material basis of this traditional Chinese medicine.

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Pre-administration of PepFect6-microRNA-146a nanocomplexes inhibits inflammatory responses in keratinocytes and in a mouse model of irritant contact dermatitis

Cited by 43 publications

References 42 publications

miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis

miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis

A retro-inverso cell-penetrating peptide for siRNA delivery

Novel mulberry silkworm cocoon-derived carbon dots and their anti-inflammatory properties

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