All-
All-
Tight junctions (TJs) in epithelial and endothelial tissues have been well studied, and a previous study suggested that the TJs of the stratum granulosum (SG) are responsible for the protective function of epithelial tissues (
To understand the molecular basis of ATRA-induced barrier dysfunction, a gene expression array was used to observe the differential gene expression in mouse skin and HaCaT cells following treatment with ATRA. Using a mouse model and a gene expression array, it was demonstrated that ATRA does, in fact, alter the structure of TJs in mouse skin. Therefore, the hypothesis was that Claudins possibly exert an essential role in barrier dysfunction during ATRA-induced skin irritation. The present study aimed to investigate the molecular mechanisms of barrier dysfunction during ATRA-induced skin irritation.
Male BALB/c mice (n=32; 8 weeks of age; weight, ~25 g) were obtained from Xi’an Jiaotong University Animal Center (Xi’an, China). The mice were fed standard chow and had access to water
The skin on the backs of the mice was shaved using an electric shaver. The mice were divided into two group: i) Treated with topical 0.1% ATRA cream (Chongqing Winbond Pharmaceutical Co., Ltd., Chongqing, China) twice a day; and ii) treated with an oil/water cream (vehicle control) twice a day. The Psoriasis Area and Severity Index (PASI) scoring system was used to assess the severity of inflammation on the back skin of the mice (
After 5 days of treatment, the mice were anesthetized using pentobarbital at 50 mg/kg. The skin from the backs of the mice, including the dermis and subcutaneous tissues, was removed. The skin was washed with pre-cooled PBS, excess fat was removed, and the specimens were placed in liquid nitrogen for RNA extraction. Subsequently, the mice were sacrificed by cervical dislocation.
ATRA-treated and untreated mouse dorsal skin specimens (1×1.5 cm) were fixed in 4% paraformaldehyde for 24 h at 4°C, dehydrated and embedded in paraffin. The samples were sectioned at 7
The specimens were cut into 1-cm blocks and dipped in ice-cold sodium cacodylate buffer solution containing 2.5% glutaraldehyde at 4°C for 24 h. The blocks were washed three times and treated with 1% osmium tetroxide at 4°C for 1 h. The samples were dehydrated using an ethanol series and embedded in Epon 812. Ultra-thin sections were stained with lead citrate for 10 min and uranyl acetate for 30 min at room temperature. Ultrastructural changes were observed by transmission electron microscopy (TEM) using a H7650 microscope (Hitachi, Ltd., Tokyo, Japan).
HaCaT cells (immortalized keratinocytes) were obtained from the Fourth Military Medical University (Shan’xi, China) and grown in RPMI-1640 (GE Healthcare, Chicago, IL, USA) with 10% fetal bovine serum (Life Technologies; Thermo Fisher Scientific, Inc., Waltham, MA, USA) and 1% penicillin-streptomycin (GE Healthcare). Short tandem repeat profiling was performed by Shanghai Zhong Qiao Xin Zhou Biotechnology Co., Ltd. (Shanghai, China) to validate the cell line. The cells were subcultured following dissociation with 0.25% trypsin/0.05% EDTA (1:1) and passaged at a ratio of 1:4 every 3 days.
HaCaT cells (5,000 cells/well) were incubated in 96-well plates for 48 h and treated by different concentrations (0.1, 0.5, 1, 5 and 10
Microarray analysis was used primarily to identify candidates that were later confirmed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and/or immunohistochemistry. The gene expression profiles in the skin of mice and in HaCaT cells treated or untreated with ATRA were compared using NimbleGen Gene Expression analysis (Nimblegen Systems Inc., Madison, WI, USA). The ds-cDNA samples were washed and labeled according to the Nimblegen Gene Expression Analysis protocol (Nimblegen Systems Inc.). A NanoDrop ND-1000 was used to quantify the cDNA following purification. Cy3 labeling was conducted using the NimbleGen One-Color DNA labeling kit (NimbleGen Systems, Inc.), according to the manufacturer’s protocol. Subsequently, 100 U Klenow fragment (New England Biolabs, Inc., Ipswich, MA, USA) and 100 pmol deoxynucleoside triphosphates were added and incubated at 37°C for 2 h. One-tenth volume of 0.5 M EDTA was added to stop the reaction. The labeled ds-cDNA was purified using isopropanol/ethanol precipitation. The microarrays were immersed in the NimbleGen hybridization buffer/hybridization component A, which was supplemented with 4
The RNAeasy Midi kit (Qiagen AB, Sollentuna, Sweden) was used to isolate the total mRNA, according to the manufacturer’s protocol. RNA (1
ATRA-treated and untreated HaCaT cells were lysed in radioimmunoprecipitation assay buffer [150 mM NaCl, 50 mM Tris-HCl (pH 8.0), 0.5% deoxycholate, 0.1% SDS, 1% Nonidet P-40 and protease inhibitor cocktail; Sigma-Aldrich; Merck KGaA] at 4°C for 1 h. Protein concentration was measured using a bicinchoninic acid protein assay kit (Beyotime Institute of Biotechnology, Haimen, China). Equal amounts of proteins (30
HaCaT cells and cryostat sections (4
All statistical analyses were conducted using SPSS 16.0 (SPSS, Inc., Chicago, IL, USA). Data are expressed as the mean ± standard deviation. All measurements were performed in triplicate from three independent experiments. The distribution was tested for normality using the Kolmogorov-Smirnov test. Statistical significance was evaluated by independent sample t-test for normally distributed data and using the Mann-Whitney U test for non-normally distributed data. P<0.05 was considered to indicate a statistically significant difference.
For the microarray data, the NimbleScan software (version 2.5; NimbleGen Systems, Inc.) was used to conduct grid alignment and analyze the expression profiles. The Robust Multichip Average (RMA) algorithm and quantile normalization in NimbleScan software were applied to the normalized expression data. The gene levels were inputted into the Agilent GeneSpring software (version 12.0; Agilent Technologies, Inc., Santa Clara, CA, USA). Fold-change filtering was applied for the identification of genes with differential expression levels. The threshold was set at-fold-change ≥2.0. The Agilent GeneSpring GX software (version 12.0; Agilent Technologies, Inc.) was used to conduct hierarchical clustering. The roles of the differentially expressed genes were determined using Gene Ontology (GO;
After 5 days of treatment, no marked alterations were detected in the control skin. Circumscribed erythema occurred after 3 days of ATRA application (n=6), with fine flat scales covering the surface of the erythema that peaked at 5 days (
Compared with control skin, keratohyalin granules were decreased in number in the SG (n=3;
With the aim of improving the understanding of the molecular mechanisms of ATRA-induced barrier dysfunction, gene expression array analysis (n=1) was used to identify candidate genes for barrier function in the mouse skin and HaCaT cells. There were 897 upregulated and 1,087 downregulated genes following treatment with ATRA in the mouse epidermis. Similarly, there were 1,220 upregulated and 905 downregulated genes following treatment with ATRA in HaCaT cells. The genes involved in epidermal barrier function were revealed by gene expression analyses and are presented in
The pathway analyses demonstrated that differentially expressed genes were significantly associated with AJs, TJs and focal adhesion in ATRA-treated epidermal tissues. The top ten pathways of up- and downregulated differentially expressed genes are presented in
Genes encoding enzymes associated with lipid metabolism were demonstrated to be induced by ATRA in the mouse epidermis. Compared with the cells, the mice exhibited significant downregulation of a subset of enzymes associated with ceramide, free fatty acids and phospholipid synthesis: i) Sphingomyelin phosphodiesterase 3 (
The dysregulation of numerous cell-cell junction-associated genes was observed in ATRA-treated mouse skin. Among these genes were components of TJs (
In ATRA-treated cells,
Immunofluorescence revealed that the intensity of Claudin-1 was not only reduced at the cell-cell contact areas, but also appeared to be discontinuous along the cell membranes of HaCaT cells treated with ATRA (
A marked reduction in the staining intensity and localization of Claudin-1 in the upper epidermal layer of skin treated with ATRA was discovered compared with control skin (n=3;
In the present study, the ATRA-associated dermatitis animal model presented erythema, scaling and dryness of the treated skin, similar to the irritation observed in ATRA-treated human skin (
In the mouse model of ATRA-stimulated dermatitis, the epidermis of the mice exhibited obvious scales, while histopathology revealed parakeratosis of the epidermis, suggesting that the epidermal differentiation was abnormal, and that the abnormal differentiation of keratinocytes led to an epidermal keratinization envelope. In the mouse gene expression profiles, it was observed that the majority of alterations occurred among EDC genes, including
Proteases, together with their inhibitors and targets, serve an essential role in desquamation (
Morphologically, the appearance of profilaggrin is consistent with the formation of keratohyalin granules. The newly-synthesized profilaggrin accumulates in keratohyalin granules with high phosphoric acid and histidine following phosphorylation. The present study demonstrated that the number of keratohyalin granules decreased significantly following ATRA treatment. Therefore, it was speculated that decreases in the number of keratohyalin granules may affect the phosphorylation and accumulation of newly-synthesized profilaggrin, affecting the production of FLG. In addition, a number of factors that are important in controlling FLG expression have been described, such as transcription factors of the AP1 family (Jun and/or Fos), POU-domain proteins, transcription factor p63, and the peroxisome-proliferator-activated-receptor (PPAR) family (
Following ATRA treatment, alterations in the ultrastructure of the epidermis were observed under an electron microscope. The images revealed that there were numerous circular vacuolated structures in the stratum corneum, which were similar to the ultrastructure of lipid droplets. Ponec
The ATRA-treated mouse skin displayed a large number of lipid droplets in certain corneocytes [similar in appearance to the droplets observed by Ponec
Mao-Qiang
Previously, lipoxygenases (LOXs) were reported to exert essential roles in regulating epithelial proliferation and/or differentiation, maintaining the permeability barrier, skin inflammation and wound healing (
TEM analysis of the mouse skin revealed an increase in the intercellular space, suggesting that the keratinocytes of the mice may have had abnormalities in the TJs. TJs function as a paracellular barrier beneath the stratum corneum (
It was observed that Claudin-2 mRNA was upregulated 2.5-fold. Telgenhoff
Notably, certain differences were observed between the
In conclusion, the results suggest that ATRA disrupts the normal morphology and ultrastructure of the mouse epidermis and exerts an essential role in the function of the epidermal barrier. Gene expression analyses revealed numerous dysregulated genes associated with the synthesis/generation of transcription factors, protease inhibitors, proteases, junctional proteins, lipids, corneocytes and cornified envelopes. ATRA not only alters the expression of Claudin-1 and -4, but also alters their localization in HaCaT cells and the murine epidermis. ATRA exerts a dual effect on epidermal barrier genes: It downregulates the expression of Claudin-1 and upregulates the expression of Claudin-4. Claudin-4 upregulation may be a compensatory response for the disrupted barrier function caused by Claudin-1 downregulation.
The present study was supported by the National Natural Science Foundation of China (grant no. 81171490) and the Fundamental Research Funds for the Central Universities (grant no. PY3A0241001016).
The datasets generated and/or analyzed during the current study are available in the GEO repository (GSE124183):
SG and JL designed the experiments. JL conducted the experiments, performed the statistical analysis and drafted the manuscript. QL performed the statistical analysis. All authors read and approved the final manuscript.
All experimental procedures were performed in accordance with the ‘Principles of Laboratory Animal Care’ (National Institutes of Health) and the guidelines of the laboratory animal care committee of Xi’an Jiaotong University (no. XJTULAC2017-733).
Not applicable.
All authors declare that they have no competing interests.
Not applicable.
all-
transmission electron microscopy
tight junctions
Gene Ontology
dimethyl sulfoxide
epidermal differentiation complex
small proline-rich region proteins
filaggrin
loricrin
Effect of ATRA on morphological changes and PASI score on the back skin of mice. (A) After 5 days of treatment, no obvious alterations were detected in the control skin. Circumscribed erythema occurred after 3 days of ATRA application and gradually expanded, presenting as fine flat scales covering the surface of the erythema and peaking at 5 days. (B) The PASI scoring system was used to assess the severity of inflammation on the back skin of the mice. *P<0.05, **P<0.01 vs. respective control. PASI, Psoriasis Area and Severity Index; ATRA, all-
Effect of ATRA on histological changes in the mouse epidermis and quantitative analysis. (A) The mice were treated with topical 0.1% ATRA cream or oil/water cream (vehicle) twice a day. The mice were sacrificed after 5 days of ATRA treatment. The stratum corneum was impaired and the number of epidermal cell layers and epidermal thickness were increased in ATRA-treated mice. Parakeratosis (black arrows), intercellular edema (triangles), and dermal inflammatory cell infiltration (white arrows) were also observed. n=6 per group. Scale bar, 100
Effect of ATRA on ultrastructural alterations in the mouse epidermis. (A) The stratum corneum was impaired and the number of epidermal cell layers and epidermal thickness were increased. The number of KGs around granular cells were decreased (arrows). (B) There were multiple lipid droplets in the corneocytes (arrows). The volume of the spinous layer cells was increased, the nucleoli were significantly larger, and the intercellular space was widened (triangles). (C) Desmosomes were reduced in number and damaged (arrows). n=3/group. A representative image is presented for each group. (D) The numbers of KGs, lipid droplets and desmosomes were quantified. KC, keratinocyte; SC, stratum corneum; SG, stratum granulosum; D, desmosome; N, nucleus; KGs, keratinocyte granules; ATRA, all-
Top ten pathways of up- and downregulated genes. The bar plots indicate the top ten (A) down- and (B) upregulated enrichment score [−log (P-value) 10] values of the significantly enriched pathways (n=1 per group). The top ten (C) down- and (D) upregulated-fold enrichment [(Count/Pop.Hits)/(List.Total/Pop.Total)] values of the significant biological processes are presented. The bar plots indicated the top ten (E) down- and (F) upregulated-fold enrichment [(Count/Pop.Hits)/(List.Total/Pop.Total)] values of the significant cellular components. The top ten (G) down- and (H) upregulated-fold enrichment [(Count/Pop.Hits)/(List.Total/Pop.Total)] values of the significant molecular functions are presented. Count, the number of differentially expressed genes associated with the listed GOID; Pop.Hits, the number of background population genes associated with the listed GOID; List.Total, the total number of differentially expressed genes; and Pop.Total, the total number of background population genes. GO, Gene Ontology.
mRNA and protein expression levels of CLDN1 and CLDN4 in immortalized keratinocyte HaCaT cells treated with ATRA. HaCaT cells were incubated with or without 1
Localization and expression of CLDN1 and CLDN4 in cultured HaCaT cells treated with ATRA. The localization of CLDN4 and CLDN1 (both red) was observed at the intercellular border in a string-like pattern in HaCaT cells treated with the vehicle. In ATRA-treated cells, CLDN4 immunofluorescence at the cell-cell contact sites appeared to be more intense compared with that in the vehicle group, while CLDN1 exhibited increased punctate localization in ATRA-treated cells. DAPI was used as a counterstain (blue). Scale bar, 20
Effect of ATRA on the localization and expression of CLDN1 and CLDN4 in mouse epidermal tissues. Following ATRA treatment, CLDN1 (red) was expressed at the cell-cell borders in the granular and spinous layers, but disappeared from the basal layers. CLDN4 (red) was expressed at the cell-cell borders in the granular layer and was enhanced in the upper spinous layer and granular layer following treatment with ATRA. DAPI was used as a counterstain (blue). Dotted lines indicate the basal layer. Scale bar, 20
Primers for reverse transcription-quantitative polymerase chain reaction.
Gene symbol | Primers |
---|---|
β-actin | F-5′-AGCAGAGAATGGAAGAGTAAA-3′ |
R-5′-ATGCTGCTTACATGTCTCGAT-3′ | |
CLDN4 | F-5′-TATGGATGAACTGCGTGGTG-3′ |
R-5′-GATGATGVTGATGATGACGAG-3′ | |
CLDN1 | F-5′-GAAGTGTATGAAGTGCTTGG-3′ |
R-5′-GGGTCATAGGGTCATAGAAT-3′ | |
CLDN2 | F-5′-GTGAAGGCAGAGATGAGAAGAGG-3′ |
R-5′-ATGGGATTTGGGCTTTTGG-3′ | |
FLG | F-5′-AGACTGGGAGGCAAGCTACAAC-3′ |
R-5′-TGGTTTGGAGTGGGATTGCT-3′ |
F, forward; R, reverse; CLDN, Claudin; FLG, filaggrin.
Downregulation of epidermal barrier-associated genes following treatment with all-
A, Cornified envelope components
| |||
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GenBank accession no. | Gene name | Gene full name | Fold downregulation |
AF510860 | FLG | Filagrin | 2.13 |
BC108980 | FOXN1 | Forkhead box N1 | 2.42 |
BC107019 | SPRR4 | Small proline-rich protein 4 | 2.67 |
BC109181 | LCE1M | Late cornified envelope 1M | 6.64 |
BC031486 | PPHLN1 | Periphilin 1 | 2.40 |
BC119192 | GPRC5D | Protein-coupled receptor, class C, group 5, member D | 20.66 |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold downregulation |
| |||
BC003472 | KRT23 | Keratin 23 | 2.67 |
BC129847 | KRT24 | Keratin 24 | 2.66 |
BC018391 | KRT25 | Keratin 25 | 6.56 |
BC116672 | KRT26 | Keratin 26 | 7.78 |
AB288231 | KRT28 | Keratin 28 | 4.28 |
BC117553 | KRT32 | Keratin 32 | 6.04 |
BC12542 | KRT34 | Keratin 34 | 101.08 |
BC100542 | KRT35 | Keratin 35 | 6.86 |
BC119521 | KRT40 | Keratin 40 | 10.11 |
BC125346 | KRT71 | Keratin 71 | 2.90 |
BC067067 | KRT73 | Keratin 73 | 4.34 |
BC107395 | KRT77 | Keratin 77 | 9.12 |
BC119366 | KRT80 | Keratin 80 | 2.21 |
AF312018 | KRT81 | Keratin 81 | 30.65 |
BC10897 | KRT82 | Keratin 82 | 10.18 |
BC152922 | KRT85 | Keratin 85 | 19.46 |
BC029257 | KRT33A | Keratin associated protein 33A | 39.26 |
NM_013570 | KRT33B | Keratin associated protein 33B | 4.79 |
NM_001085526 | KRTAP1-2 | Keratin associated protein 1-3 | 13.42 |
XM_894811 | KRTAP3-1 | Keratin associated protein 3-1 | 29.03 |
BC156698 | KRTAP4-2 | Keratin associated protein 4-2 | 19.09 |
NM_026834 | KRTAP4-6 | Keratin associated protein 4-6 | 24.72 |
BC115508 | KRTAP4-7 | Keratin associated protein 4-7 | 33.02 |
NM_001085547 | KRTAP4-8 | Keratin associated protein 4-8 | 43.14 |
NM_001085548 | KRTAP4-9 | Keratin associated protein 4-9 | 24.62 |
BC016249 | KRTAP4-16 | Keratin associated protein 4-16 | 42.20 |
NM_015809 | KRTAP5-4 | Keratin associated protein 5-4 | 19.54 |
NM_027771 | KRTAP7-1 | Keratin associated protein 7-1 | 137.50 |
AK133727 | KRTAP8-1 | Keratin associated protein 8-1 | 18.92 |
BC116210 | KRTAP9-1 | Keratin associated protein 9-1 | 11.56 |
BC156686 | KRTAP9-3 | Keratin associated protein 9-3 | 35.46 |
NM_001085527 | KRTAP9-5 | Keratin associated protein 9-5 | 12.10 |
BC116219 | KRTAP15 | Keratin associated protein 15 | 60.31 |
BC116200 | KRTAP19-4 | Keratin associated protein 19-4 | 10.75 |
BC115545 | KRTAP19-3 | Keratin associated protein 19-3 | 8.54 |
BC132612 | KRTAP6-5 | Keratin associated protein 6-5 | 14.96 |
BC132658 | KRTAP16-3 | Keratin associated protein 16-3 | 39.91 |
BC128283 | KRTAP26-1 | Keratin associated protein 26-1 | 6.51 |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold downregulation |
| |||
AK003689 | LYPLA2 | Lysophospholipase II | 2.00 |
BC027524 | PLA2G2E | Phospholipase A2, group IIE | 2.60 |
BC148434 | PLCH2 | Phospholipase C eta 2 | 2.13 |
BC047281 | AGPAT4 | 1-acylglycerol-3-phosphate O-acyltransferase 4 | 3.81 |
BC031987 | AGPAT5 | 1-acylglycerol-3-phosphate O-acyltransferase 5 | 3.17 |
AK019476 | SMPD3 | Sphingomyelin Phosphodiesterase 3 neutral | 2.15 |
AK088962 | SMPD2 | Sphingomyelin phosphodiesterase 2 neutral | 2.10 |
BC013751 | ALOX12E | Arachidonate lipoxygenase | 3.90 |
BC043059 | LASS5/Cers5 | Epidermal ceramide synthase 5 | 2.82 |
BC075627 | DGKK | Diacylglycerol kinase κ | 3.89 |
BC021597 | APOM | Apolipoprotein M | 2.58 |
BC006863 | FAAH | Fatty acid amide hydrolase | 2.22 |
BC071266 | FADS3 | Fatty acid desaturase 3 | 2.53 |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold downregulation |
| |||
AY427554 | GJA1 | Gap junction protein α1 | 2.00 |
AY390399 | GJA3 | Gap junction protein α3 | 2.57 |
BC024387 | GJB3 | Gap junction protein β3 | 2.77 |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold downregulation |
| |||
AK165750 | PRKCZ | Protein kinase C ζ | 2.37 |
DQ682659 | MARVELD2 | MARVEL domain containing 2 | 3.81 |
AK190015 | TJAP1 | Tight junction associated protein 1 | 2.08 |
BC049662 | MPP7 | Membrane palmitoylated protein 7 | 2.11 |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold downregulation |
| |||
BC020144 | DSG2 | Desmoglein 2 | 4.48 |
Upregulation of epidermal barrier-associated genes following treatment with all-
A, Cornified envelope components
| |||
---|---|---|---|
GenBank accession no. | Gene name | Gene full name | Fold upregulation |
BC115788 | LCE3B | Late cornified envelope 3B | 3.17 |
BC119239 | LCE3C | Late cornified envelope 3C | 5.35 |
BC125542 | SPRR2J | Small proline-rich protein 2J | 2.38 |
BC130233 | SPRR2G | Small proline-rich protein 2G | 3.57 |
BC078629 | S100A8 | S100 calcium binding protein A8 (calgranulin A) | 3.31 |
AK143826 | S100A9 | S100 calcium binding protein A9 (calgranulin B) | 3.81 |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold upregulation |
| |||
BC031119 | KLK6 | Kallikrein related-peptidase 6 | 3.22 |
BC002100 | KLK10 | Kallikrein related-peptidase 10 | 2.90 |
XM_893506 | KLK12 | Kallikrein related-peptidase 12 | 2.50 |
BC054091 | SERPINE1 | Serine (cysteine) proteinase inhibitor, clade E, member 1 | 2.15 |
BC010675 | SERPINE2 | Serine (cysteine) proteinase inhibitor, clade E, member 2 | 2.98 |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold upregulation |
| |||
BC010829 | ACNAT2 | Acyl-coenzyme A amino acid N-acyltransferase 2 | 2.03 |
DQ469311 | ACNAT1 | Acyl-coenzyme A amino acid N-acyltransferase 1 | 2.94 |
AK171255 | ACOT11 | Acyl-CoA thioesterase 11 | 3.73 |
BC050828 | UGCG | UDP-glucose ceramide glucosyltransferase | 2.21 |
BC060600 | PLA2G4E | Phospholipase A2, group IVE | 2.39 |
BC003470 | PLA1A | Phospholipase A1 member A | 2.06 |
BC003943 | DPAGT1 | Dolichyl-phosphate (UDP-N-acetylglucosamine) glycerol | 2.10 |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold upregulation |
| |||
BC015252 | CLDN2 Claudin-2 | 2.43 | |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold upregulation |
| |||
BC070398 | PPARδ | Peroxisome proliferator activator receptor δ | 2.00 |
Downregulation of epidermal barrier-associated genes following treatment with all-
A, Intermediate filament
| |||
---|---|---|---|
GenBank accession no. | Gene name | Gene full name | Fold downregulation |
NM_181619 | KRTAP21-1 | Keratin associated protein 21-1 | 2.38 |
NM_033448 | KRT71 | Keratin 71 | 2.00 |
BC024292 | KRT5 | Keratin 5 | 2.22 |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold downregulation |
| |||
BC069417 | SERPINB7 | Serpin family B member 7 | 3.15 |
NM_000185 | SERPIND1 | Serpin family D member 1 | 2.36 |
NM_007173 | PRSS23 | Serine protease 23 | 4.13 |
NM_022046 | KLK14 | Kallikrein related peptidase 10 | 2.29 |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold downregulation |
| |||
AK128686 | PDZD2 | PDZ domain containing 2 | 2.15 |
Upregulation of epidermal barrier-associated genes following treatment with all-
A, Intermediate filament
| |||
---|---|---|---|
GenBank accession no. | Gene name | Gene full name | Fold upregulation |
NM_002275 | KRT15 | Keratin 15 | 2.07 |
BC072018 | KRT17 | Keratin 17 | 2.68 |
AB096945 | KRTAP19-4 | Keratin associated protein 19-4 | 2.07 |
BC101555 | KRTAP7-1 | Keratin associated protein 7-1 (gene/pseudogene) | 2.05 |
NM_032524 | KRTAP4-4 | Keratin associated protein 4-4 | 2.16 |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold upregulation |
| |||
NM_001085 | SERPINA3 | Serpin family A member 3 | 12.30 |
NM_000624 | SERPINA5 | Serpin family A member 5 | 2.03 |
BC034528 | SERPINB8 | Serpin family B member 8 | 2.11 |
NM_000934 | SERPINF2 | Serpin family F member 2 | 2.06 |
NM_002575 | SERPINB2 | Serpin family B member 2 | 2.17 |
BC009726 | PRSS22 | Serine protease 22 | 4.26 |
AF335478 | KLK3 | Kallikrein related peptidase 3 | 2.27 |
NM_001012964 | KLK6 | Kallikrein related peptidase 6 | 2.95 |
NM_002776 | KLK10 | Kallikrein related peptidase 10 | 2.44 |
NM_006853 | KLK11 | Kallikrein related peptidase 11 | 2.43 |
NM_015596 | KLK13 | Kallikrein related peptidase 13 | 2.80 |
NM_017509 | KLK15 | Kallikrein related peptidase 15 | 2.02 |
| |||
| |||
GenBank accession no. | Gene name | Gene full name | Fold upregulation |
| |||
BC029886 | OCLN Occludin | 2.63 | |
NM_001305 | CLDN4 Claudin-4 | 2.02 |