Mesenchymal Stem Cells and Extracellular Vesicles Derived from Canine Adipose Tissue Ameliorates Inflammation, Skin Barrier Function and Pruritus by Reducing JAK/STAT Signaling in Atopic Dermatitis
Abstract
:1. Introduction
2. Results
2.1. Characterization of cASCs and cASC-EVs
2.2. cASCs and cASC-EVs Alleviate Atopic Dermatitis Induced by DNCB Treatment
2.3. cASCs and cASC-EVs Ameliorated Skin Inflammation in DNCB-Induced Atopic Dermatitis Mice
2.4. cASCs and cASC-EVs Promote Skin Barrier Repair in DNCB-Induced Atopic Dermatitis Mice
2.5. cASCs and cASC-EVs Suppressed IL-31-Mediated Pruritus and Phosphorylated STATs in DNCB-Induced Atopic Dermatitis Mice
3. Discussion
4. Materials and Methods
4.1. Isolation, Culture, and Characterization of cASC
4.2. Isolation and Characterization of cASC-EV
4.3. Animal Care and Induction of AD Model
4.4. Measurement of Dermatitis Score and Epidermal Thickness
4.5. Measurement of Total Serum IgE and Inflammatory Cytokines
4.6. Histological Examination
4.7. RNA Extraction and Real-Time PCR
4.8. Western Blot Analysis
4.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Mean ± SD | Group 1 (Normal) | Group 2 (DNCB + Vehicle) | Group 3 (DNCB + EV) | Group 4 (DNCB + cASC) | p-Value * (Group 2–3) | p-Value * (Group 2–4) |
---|---|---|---|---|---|---|
Epidermal Thickness (Skin, μm) | 23.8 ± 3.2 | 130.0 ± 23.9 | 88.4 ± 13.5 | 83.3 ± 20.8 | 0.002 | 0.003 |
Epidermal Thickness (Ear, μm) | 13.7 ± 3.5 | 76.5 ± 36.8 | 37.0 ± 14.7 | 24.4 ± 3.9 | 0.044 | 0.018 |
Serum IgE (μg/mL) | 42.4 ± 10.9 | 867.5 ± 194.6 | 588.9 ± 95.8 | 437.6 ± 123.6 | 0.016 | 0.002 |
Mast cell count (Skin, ea) | 12.7 ± 5.3 | 57.0 ± 8.2 | 32.7 ± 12.4 | 34.7 ± 11.9 | 0.003 | 0.004 |
Mast cell count (Ear, ea) | 11.7 ± 4.2 | 31.3 ± 4.2 | 20.8 ± 2.4 | 20.5 ± 2.3 | <0.001 | <0.001 |
IL-4 mRNA (fold) | 1.0 ± 0.5 | 2.5 ± 1.4 | 1.4 ± 0.1 | 1.7 ± 0.2 | 0.094 | 0.197 |
IL-13 mRNA (fold) | 1.0 ± 0.6 | 2.8 ± 1.3 | 1.3 ± 0.3 | 1.9 ± 0.6 | 0.039 | 0.163 |
IL-31 mRNA (fold) | 1.0 ± 0.4 | 4.2 ± 2.2 | 1.0 ± 0.5 | 1.5 ± 0.5 | 0.016 | 0.030 |
TSLP mRNA (fold) | 1.0 ± 0.4 | 5.6 ± 2.3 | 1.3 ± 1.1 | 0.6 ± 0.4 | 0.002 | 0.003 |
K1 mRNA (fold) | 1.0 ± 0.2 | 0.6 ± 0.2 | 0.9 ± 0.1 | 1.0 ± 0.2 | 0.005 | 0.002 |
RANTES mRNA (fold) | 1.0 ± 0.5 | 3.6 ± 1.1 | 1.6 ± 1.0 | 1.2 ± 0.3 | 0.007 | 0.002 |
TEWL (g/m2/h) | 11.8 ± 2.0 | 39.7 ± 6.9 | 26.5 ± 3.6 | 22.5 ± 3.5 | 0.002 | <0.001 |
Hydration (A.U.) | 49.4 ± 5.6 | 33.5 ± 4.1 | 39.6 ± 7.9 | 41.4 ± 2.5 | 0.121 | 0.002 |
FLG mRNA (fold) | 1 ± 0.1 | 0.5 ± 0.1 | 0.9 ± 0.3 | 0.6 ± 0.1 | 0.009 | 0.062 |
LOR mRNA (fold) | 1 ± 0.3 | 0.6 ± 0.2 | 0.8 ± 0.1 | 0.8 ± 0.1 | 0.039 | 0.072 |
INV mRNA (fold) | 1.0 ± 0.4 | 0.5 ± 0.2 | 0.7 ± 0.1 | 0.8 ± 0.2 | 0.068 | 0.063 |
TRPA1 mRNA (fold) | 1.0 ± 0.4 | 2.1 ± 0.3 | 1.4 ± 0.1 | 1.5 ± 0.1 | 0.003 | 0.008 |
IL-31RA mRNA (fold) | 1.0 ± 0.4 | 1.7 ± 0.4 | 1.3 ± 0.1 | 1.4 ± 0.1 | 0.038 | 0.128 |
OSMR mRNA (fold) | 1.0 ± 0.6 | 3.3 ± 1.7 | 0.9 ± 0.5 | 0.6 ± 0.2 | 0.016 | 0.012 |
p-STAT1/STAT1 (fold) | 1.0 ± 0.1 | 4.0 ± 0.4 | 0.7 ± 0.2 | 0.8 ± 0.2 | <0.001 | <0.001 |
p-STAT3/STAT3 (fold) | 1.0 ± 0.1 | 3.1 ± 0.2 | 2.0 ± 0.5 | 1.3 ± 0.7 | 0.031 | 0.013 |
Median [IQR] (Min–Max) | Group 1 (Normal) | Group 2 (DNCB + Vehicle) | Group 3 (DNCB + EV) | Group 4 (DNCB + cASC) | p-Value ** (Group 2–3) | p-Value ** (Group 2–4) |
---|---|---|---|---|---|---|
Dermatitis Score | 0 | 8.5 [8.0–9.0] (3.0–10.0) | 4.0 [4.0–4.0] (3.0–6.0) | 3 [3.0–3.8] (3.0–4.0) | 0.040 | 0.019 |
TARC mRNA (fold) | 0.9 [0.8–1.2] (0.5–1.7) | 5.0 [3.4–5.4] (1.8–8.3) | 0.7 [0.6–1.4] (0.3–3.9) | 1.8 [1.7–1.8] (1.6–1.9) | 0.010 | 0.016 |
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Kim, S.Y.; Yoon, T.H.; Na, J.; Yi, S.J.; Jin, Y.; Kim, M.; Oh, T.-H.; Chung, T.-W. Mesenchymal Stem Cells and Extracellular Vesicles Derived from Canine Adipose Tissue Ameliorates Inflammation, Skin Barrier Function and Pruritus by Reducing JAK/STAT Signaling in Atopic Dermatitis. Int. J. Mol. Sci. 2022, 23, 4868. https://doi.org/10.3390/ijms23094868
Kim SY, Yoon TH, Na J, Yi SJ, Jin Y, Kim M, Oh T-H, Chung T-W. Mesenchymal Stem Cells and Extracellular Vesicles Derived from Canine Adipose Tissue Ameliorates Inflammation, Skin Barrier Function and Pruritus by Reducing JAK/STAT Signaling in Atopic Dermatitis. International Journal of Molecular Sciences. 2022; 23(9):4868. https://doi.org/10.3390/ijms23094868
Chicago/Turabian StyleKim, Sung Youl, Tae Hong Yoon, Jungtae Na, Seong Joon Yi, Yunseok Jin, Minji Kim, Tae-Ho Oh, and Tae-Wook Chung. 2022. "Mesenchymal Stem Cells and Extracellular Vesicles Derived from Canine Adipose Tissue Ameliorates Inflammation, Skin Barrier Function and Pruritus by Reducing JAK/STAT Signaling in Atopic Dermatitis" International Journal of Molecular Sciences 23, no. 9: 4868. https://doi.org/10.3390/ijms23094868