scholarly journals Indirubin attenuates mouse psoriasis-like skin lesion in a CD274-dependent manner: an achievement of RNA sequencing

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Xiaochun Xue ◽  
Jianhua Wu ◽  
Junhui Li ◽  
Jianguo Xu ◽  
Haiying Dai ◽  
...  
Keyword(s):  
Network Analysis ◽  
Skin Lesion ◽  
Candidate Genes ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Regulatory Mechanisms ◽  
Epidermal Keratinocytes ◽  
Dependent Manner ◽  
Human Epidermal Keratinocytes ◽  
Ifn Γ

It was previously reported that the expression of CD274 was down-regulated in psoriatic epidermis, leading to immune disorders of psoriasis. However, the regulatory mechanisms of CD274 were rarely elucidated. We aimed to explore the regulatory mechanisms of CD274. Skin samples were collected from 18 patients with psoriasis vulgaris and 9 healthy participants for RNA sequencing. Candidate genes were chosen based on degree and k-core difference of genes in the co-expression network. The relations between candidate genes and CD274 were validated by flow cytometry and real-time PCR in primary human epidermal keratinocytes. The therapeutic effect of indirubin was assessed in an imiquimod-treated mouse model. Interferon-γ (IFN-γ), cyclin-dependent kinase (CDK) 1, Toll-like receptor 3 (TLR3), TLR4 and interleukin (IL)-17A were considered as candidate genes. In primary human epidermal keratinocytes, the level of CD274 was obviously increased under the stimulation of IFN-γ and CDK1 inhibitor (indirubin), independent of TLR4, TLR3 or IL-17A. Indirubin alleviated the severity of psoriatic mice in a CD274-dependent manner. Co-expression network analysis served as an effective method for the exploration of molecular mechanisms. We demonstrated for the first time that CD274 was the regulator of indirubin-mediated effect on mouse psoriasis-like skin lesion based on co-expression network analysis, contributing to the alleviation of mouse psoriasis-like skin lesion.

scholarly journals miR-136 Modulates TGF-β1-Induced Proliferation Arrest by Targeting PPP2R2A in Keratinocytes

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Dianbao Zhang ◽  
Jing Wang ◽  
Zhe Wang ◽  
Tao Zhang ◽  
Ping Shi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Skin Wound ◽  
Luciferase Reporter ◽  
Epidermal Keratinocytes ◽  
Dependent Manner ◽  
Hacat Cells ◽  
Skin Wound Healing ◽  
Human Epidermal Keratinocytes ◽  
Reporter Assays ◽  
Normal Human

Keratinocytes proliferation is critical for the capacity to heal wounds and accumulating evidences have proved that dysregulation of microRNAs is involved in proliferation of keratinocytes. However, the molecular mechanisms remain to be completely elucidated. Here, we show that miR-136 was significantly decreased by TGF-β1 treatment in HaCaT cells and normal human epidermal keratinocytes (NHEK), and it was a Smad3-dependent manner. By cell proliferation assay and cell cycle analysis, we found that reintroduction of miR-136 by transfection, as well as PPP2R2A silencing, counteracted TGF-β-induced proliferation arrest in HaCaT cells. Further, PPP2R2A was verified as a direct target of miR-136 by dual-luciferase reporter assays and Western blotting. These data suggest that miR-136 may play an important role during TGF-β1-induced proliferation arrest by targeting PPP2R2A in keratinocytes, which might represent a potential target for improving skin wound healing.

scholarly journals Distinct Amino Acid Availability-Dependent Regulatory Mechanisms of MepS and MepM Levels in Escherichia coli

2021 ◽  
Vol 12 ◽  
Author(s):  
Yung Jae Kim ◽  
Byoung Jun Choi ◽  
Si Hyoung Park ◽  
Han Byeol Lee ◽  
Ji Eun Son ◽  
...  
Keyword(s):  
Amino Acid ◽  
Minimal Medium ◽  
Molecular Mechanisms ◽  
Aromatic Amino Acids ◽  
Normal Growth ◽  
Regulatory Mechanisms ◽  
Dependent Manner ◽  
Bacterial Physiology ◽  
Protein Levels ◽  
Amino Acid Availability

Peptidoglycan (PG) hydrolases play important roles in various aspects of bacterial physiology, including cytokinesis, PG synthesis, quality control of PG, PG recycling, and antibiotic resistance. However, the regulatory mechanisms of their expression are poorly understood. In this study, we have uncovered novel regulatory mechanisms of the protein levels of the synthetically lethal PG endopeptidases MepS and MepM, which are involved in PG synthesis. A mutant defective for both MepS and MepM was lethal in an amino acid-rich medium, whereas it exhibited almost normal growth in a minimal medium, suggesting the expendability of MepS and MepM in a minimal medium. Protein levels of MepS and MepM dramatically decreased in the minimal medium. Although MepM was revealed as a substrate of Prc, a periplasmic protease involved in the proteolysis of MepS, only the decrease in the MepS level in the minimal medium was affected by the prc depletion. Phenotypic and biochemical analyses showed that the presence of aromatic amino acids in the medium induced the accumulation of MepS, but not MepM, while the presence of glutamate increased the level of MepM, but not MepS. Together, these results demonstrate that the protein levels of the two major PG endopeptidases are regulated in an amino acid availability-dependent manner, but their molecular mechanisms and signaling are significantly distinct.

scholarly journals Nickel Nanoparticles Induce the Synthesis of a Tumor-Related Polypeptide in Human Epidermal Keratinocytes

Nanomaterials ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 992
Author(s):  
Javier Jiménez-Lamana ◽  
Simon Godin ◽  
Gerard Aragonès ◽  
Cinta Bladé ◽  
Joanna Szpunar ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Nickel Nanoparticles ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Nickel Allergy ◽  
Skin Cells ◽  
Nickel Binding ◽  
Nickel Compounds ◽  
Linear Behavior ◽  
Genotoxic Carcinogens

Although nickel allergy and carcinogenicity are well known, their molecular mechanisms are still uncertain, thus demanding studies at the molecular level. The nickel carcinogenicity is known to be dependent on the chemical form of nickel, since only certain nickel compounds can enter the cell. This study investigates, for the first time, the cytotoxicity, cellular uptake, and molecular targets of nickel nanoparticles (NiNPs) in human skin cells in comparison with other chemical forms of nickel. The dose-response curve that was obtained for NiNPs in the cytotoxicity assays showed a linear behavior typical of genotoxic carcinogens. The exposure of keratinocytes to NiNPs leads to the release of Ni2+ ions and its accumulation in the cytosol. A 6 kDa nickel-binding molecule was found to be synthesized by cells exposed to NiNPs at a dose corresponding to medium mortality. This molecule was identified to be tumor-related p63-regulated gene 1 protein.

scholarly journals Differential and Overlapping Effects of 20,23(OH)2D3 and 1,25(OH)2D3 on Gene Expression in Human Epidermal Keratinocytes: Identification of AhR as an Alternative Receptor for 20,23(OH)2D3

2018 ◽  
Vol 19 (10) ◽  
pp. 3072 ◽  
Author(s):  
Andrzej Slominski ◽  
Tae-Kang Kim ◽  
Zorica Janjetovic ◽  
Anna Brożyna ◽  
Michal Żmijewski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Modeling ◽  
Vitamin D3 ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Canonical Pathway ◽  
Epidermal Keratinocytes ◽  
Hydroxyl Groups ◽  
Dependent Manner ◽  
Human Epidermal Keratinocytes

A novel pathway of vitamin D activation by CYP11A has previously been elucidated. To define the mechanism of action of its major dihydroxy-products, we tested the divergence and overlap between the gene expression profiles of human epidermal keratinocytes treated with either CYP11A1-derived 20,23(OH)2D3 or classical 1,25(OH)2D3. Both secosteroids have significant chemical similarity with the only differences being the positions of the hydroxyl groups. mRNA was isolated and examined by microarray analysis using Illumina’s HumanWG-6 chip/arrays and subsequent bioinformatics analyses. Marked differences in the up- and downregulated genes were observed between 1,25(OH)2D3- and 20,23(OH)2D3-treated cells. Hierarchical clustering identified both distinct, opposite and common (overlapping) gene expression patterns. CYP24A1 was a common gene strongly activated by both compounds, a finding confirmed by qPCR. Ingenuity pathway analysis identified VDR/RXR signaling as the top canonical pathway induced by 1,25(OH)2D3. In contrast, the top canonical pathway induced by 20,23(OH)2D3 was AhR, with VDR/RXR being the second nuclear receptor signaling pathway identified. QPCR analyses validated the former finding by revealing that 20,23(OH)2D3 stimulated CYP1A1 and CYP1B1 gene expression, effects located downstream of AhR. Similar stimulation was observed with 20(OH)D3, the precursor to 20,23(OH)2D3, as well as with its downstream metabolite, 17,20,23(OH)3D3. Using a Human AhR Reporter Assay System we showed marked activation of AhR activity by 20,23(OH)2D3, with weaker stimulation by 20(OH)D3. Finally, molecular modeling using an AhR LBD model predicted vitamin D3 hydroxyderivatives to be good ligands for this receptor. Thus, our microarray, qPCR, functional studies and molecular modeling indicate that AhR is the major receptor target for 20,23(OH)2D3, opening an exciting area of investigation on the interaction of different vitamin D3-hydroxyderivatives with AhR and the subsequent downstream activation of signal transduction pathways in a cell-type-dependent manner.

scholarly journals Pyridoxine Stimulates Filaggrin Production in Human Epidermal Keratinocytes

2021 ◽  
Author(s):  
Miyuki Fujishiro ◽  
Shoichi Yahagi ◽  
Shota Takemi ◽  
Takafumi Sakai ◽  
ichiro sakata
Keyword(s):  
Pyridoxal Phosphate ◽  
Seborrheic Dermatitis ◽  
Epidermal Differentiation ◽  
Disulfonic Acid ◽  
Epidermal Keratinocytes ◽  
Marker Genes ◽  
Dependent Manner ◽  
Human Epidermal Keratinocytes ◽  
Concentration Dependent Manner ◽  
Protein Levels

Abstract Pyridoxine (PN), one of the vitamers of vitamin B6, plays an important role in the maintenance of epidermal function and is used to treat acne and rough skin. Clinical studies have revealed that PN deficiency causes skin problems such as seborrheic dermatitis and stomatitis. However, the detailed effects of PN and its mechanism of action in epidermal function are poorly understood. In this study, we examined the effects of PN on epidermal function in normal human epidermal keratinocytes and found that PN specifically causes an increase in the expression of profilaggrin mRNA, among marker genes of terminal epidermal differentiation. In addition, PN treatment caused an increase in the production of filaggrin protein in a concentration-dependent manner. Treatment with P2x purinoceptor antagonists, namely, pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium salt hydrate and TNP-ATP hydrate, induced an increase in the filaggrin protein levels. Moreover, we showed that elevated filaggrin production induced upon PN treatment was suppressed by ATP (known as P2x purinoceptor agonist). This study is the first to report that PN causes an increase in filaggrin transcription and production, and these results suggest that PN-induced filaggrin production may be a useful target as a daily care component in atopic dermatitis, wherein filaggrin levels are specifically reduced.

Amygdalin Analogues Inhibit IFN-γ Signalling and Reduce the Inflammatory Response in Human Epidermal Keratinocytes

Inflammation ◽  
2013 ◽  
Vol 36 (6) ◽  
pp. 1316-1326 ◽  
Author(s):  
Iole Paoletti ◽  
Vincenza De Gregorio ◽  
Adone Baroni ◽  
Maria Antonietta Tufano ◽  
Giovanna Donnarumma ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Ifn Γ

Regulatory mechanisms for semaphorin 3A in human epidermal keratinocytes.

2013 ◽  
Vol 69 (2) ◽  
pp. e11
Author(s):  
Yayoi Kamata ◽  
Mitsutoshi Tominaga ◽  
Atsuko Kamo ◽  
Suhandy Tengara ◽  
Kenji Takamori
Keyword(s):  
Regulatory Mechanisms ◽  
Epidermal Keratinocytes ◽  
Semaphorin 3A ◽  
Human Epidermal Keratinocytes
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