Enhancement of elastin expression by transdermal administration of sialidase isozyme Neu2

Minami, Akira; Fujita, Yuka; Goto, Jun; Iuchi, Ayano; Fujita, Kosei; Mikami, Yuji; Shiratori, Mako; Ishii, Ami; Mitragotri, Samir; Iwao, Yasunori; Kanazawa, Hiroaki; Kurebayashi, Yuuki; Takahashi, Toshifumi; Otsubo, Tadamune; Ikeda, Kiyoshi; Suzuki, Takashi

doi:10.1038/s41598-021-82820-1

Cited by 9 publications

(6 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reportedly, elastin, filaggrin, loricrin, and collagen in the skin decrease with age in normal mice. [33][34][35][36][37] Similar results were also found in the SAMP mice, suggesting that 8-month-old SAMP mice could serve as a tool for skin aging research.…”

Section: Discussionsupporting

confidence: 70%

Expression analysis of genes important for maintaining skin function in a senescence‐accelerated mouse prone model

Shinozaki,

Ikarashi,

Tabata

et al. 2023

Geriatrics Gerontology Int

View full text Add to dashboard Cite

AimSenescence‐accelerated mouse prone (SAMP) mice can reproduce the same conditions as normal aging mice in a short period. Although SAMP mice have been widely used in aging research, research on skin function in SAMP mice is lacking. In this study, to investigate the skin function of SAMP mice, we analyzed the expression of genes important for maintaining skin function.MethodsEight‐month‐old SAMP mice and senescence‐accelerated mouse resistant (SAMR) mice with normal aging were used. The expression levels of various functional genes in the skin were analyzed.ResultsThe dermal water content of SAMP mice was significantly lower than that of SAMR mice, indicating dry skin. The mRNA expression levels of elastin (Ela), filaggrin (Flg), loricrin (Lor), collagen type I alpha 1 chain (Col1a1) and Col1a2 in the skin of SAMP mice were all significantly decreased compared with those of SAMR mice. Hyaluronan‐degrading enzyme (Hyal1) expression levels in SAMP mice were similar to those in SAMR mice, but hyaluronan synthase (Has2) levels were significantly decreased. In addition, the expression level of aquaporin‐3 in the skin of SAMP mice was significantly decreased at both the mRNA and protein levels.ConclusionsIn the skin of SAMP mice, the expression levels of various skin function‐regulating genes were decreased, and this phenomenon might cause skin dryness. The SAMP mouse could be a tool for analyzing skin aging. Geriatr Gerontol Int 2023; ••: ••–••.

show abstract

Section: Discussionsupporting

confidence: 70%

Expression analysis of genes important for maintaining skin function in a senescence‐accelerated mouse prone model

Shinozaki,

Ikarashi,

Tabata

et al. 2023

Geriatrics Gerontology Int

View full text Add to dashboard Cite

show abstract

“…Using Venn diagram, we established the intersection of lactate up‐regulated differential expressed gene sets and the genes annotated to promoter regions, and four genes (Neu2, Syk, Nhsl2 and Adgrg3) were identified as potential targets of H3K9la (Figure 4F ). Of the four genes, only Neu2 is related to muscle differentiation based on GO annotation and literature reports 15 , 16 , 17 , 18 , 19 , 31 , 32 ; we thus tested whether Neu2 is involved in H3K9la‐mediated myogenesis.…”

Section: Resultsmentioning

confidence: 99%

“…Neuraminidase 2 (Neu2) is a cytosolic sialidase that have been reported to play an important role in skeletal muscle differentiation 17–19,31 . However, it remains unclear whether Neu2 is involved in lactate‐induced muscle differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…Neuraminidase 2 (Neu2) is a cytosolic sialidase that have been reported to play an important role in skeletal muscle differentiation. 17 , 18 , 19 , 31 However, it remains unclear whether Neu2 is involved in lactate‐induced muscle differentiation. In this study, we first demonstrated that lactate treatment specifically increased the expression of Neu2 during myoblast differentiation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Lactate promotes myogenesis via activating H3K9 lactylation‐dependent up‐regulation of Neu2 expression

Dai,

Wu,

Liu

et al. 2023

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

BackgroundLactate, a glycolytic metabolite mainly produced in muscles, has been suggested to regulate myoblast differentiation, although the underlying mechanism remains elusive. Recently, lactate‐mediated histone lactylation is identified as a novel epigenetic modification that promotes gene transcription.MethodsWe used mouse C2C12 cell line and 2‐month‐old male mice as in vitro and in vivo models, respectively. These models were treated with lactate to explore the biological function and latent mechanism of lactate‐derived histone lactylation on myogenic differentiation by quantitative real‐time PCR, western blotting, immunofluorescence staining, chromatin immunoprecipitation, cleavage under targets and tagmentation assay and RNA sequencing.ResultsUsing immunofluorescence staining and western blotting, we proposed that lactylation might occur in the histones. Inhibition of lactate production or intake both impaired myoblast differentiation, accompanied by diminished lactylation in the histones. Using lactylation site‐specific antibodies, we demonstrated that lactate preferentially increased H3K9 lactylation (H3K9la) during myoblast differentiation (CT VS 5, 10, 15, 20, 25 mM lactate treatment, P = 0.0012, P = 0.0007, and the rest of all P < 0.0001). Notably, inhibiting H3K9la using P300 antagonist could block lactate‐induced myogenesis. Through combined omics analysis using cleavage under targets and tagmentation assay and RNA sequencing, we further identified Neu2 as a potential target gene of H3K9la. IGV software analysis (P = 0.0013) and chromatin immunoprecipitation‐qPCR assay (H3K9la %Input, LA group = 9.0076, control group = 2.7184, IgG = 0.3209) confirmed that H3K9la is enriched in the promoter region of Neu2. Moreover, siRNAs or inhibitors against Neu2 both abrogated myoblast differentiation despite lactate treatment, suggesting that Neu2 is required for lactate‐mediated myoblast differentiation.ConclusionsOur findings provide novel understanding of histone lysine lactylation, suggesting its role in myogenesis, and as potential therapeutic targets for muscle diseases.

show abstract

“…We previously reported that an IL composed of choline and geranic acid (CAGE) increased the solubility of a poorly water-soluble flavonoid nobiletin by 450-fold and promoted its transdermal permeation . We have also demonstrated the transdermal delivery of insulin and sialidase isozyme Neu2 and resultant exertion of their biological activities in vivo , , indicating potential usefulness of ILs in pharmaceutical applications. As another approach to drug delivery with ILs, Kim et al reported that a lipoidal IL composed of choline and oleate efficiently solvates verteporfin, a water-insoluble anticancer drug, and subsequently forms stable nanocomplexes <100 nm .…”

Section: Introductionmentioning

confidence: 98%

Development of Edaravone Ionic Liquids and Their Application for the Treatment of Cerebral Ischemia/Reperfusion Injury

2023

Self Cite

View full text Add to dashboard Cite

Preparation of the ionic liquid (IL) form of active pharmaceutical ingredients (APIs), termed API-IL, has attracted attention because it can improve upon certain disadvantages of APIs, such as poor water solubility and low stability. Edaravone (3methyl-1-phenyl-2-pyrazolin-5-one) is a clinically approved cerebroprotective agent against ischemic stroke and amyotrophic lateral sclerosis, while new formulations that enable improvement of its physicochemical properties and biodistribution are desired. Herein, we report a newly developed API-IL of edaravone (edaravone-IL), in which edaravone is used as an anionic molecule. We investigated the physicochemical properties of edaravone-IL and its therapeutic effect against cerebral ischemia/reperfusion (I/R) injury, a secondary injury after an ischemic stroke. Among the cationic molecules used for edaravone-IL preparation, the IL prepared with tetrabutylphosphonium cation existed as a liquid at room temperature, and significantly increased the water solubility of edaravone without decreasing its antioxidative activity. Importantly, edaravone-IL formed negatively charged nanoparticles upon suspension in water. Intravenous administration of edaravone-IL showed significantly higher blood circulation time and lower distribution in the kidney compared with edaravone solution. Moreover, edaravone-IL significantly suppressed brain cell damage and motor functional deficits in model rats of cerebral I/R injury and showed comparable cerebroprotective effect to edaravone. Taken together, these results suggest that edaravone-IL could be a new form of edaravone with superior physicochemical properties and could be useful for the treatment of cerebral I/R injury.

show abstract

Enhancement of elastin expression by transdermal administration of sialidase isozyme Neu2

Cited by 9 publications

References 45 publications

Expression analysis of genes important for maintaining skin function in a senescence‐accelerated mouse prone model

Expression analysis of genes important for maintaining skin function in a senescence‐accelerated mouse prone model

Lactate promotes myogenesis via activating H3K9 lactylation‐dependent up‐regulation of Neu2 expression

Development of Edaravone Ionic Liquids and Their Application for the Treatment of Cerebral Ischemia/Reperfusion Injury

Contact Info

Product

Resources

About