| RRC ID |
73859
|
| Author |
Yi-Qun Zhang, Ta Xiao, Chang-Jun Song, Yang-Ying Ke, Xiang Gao, Min Li, Heng Gu, Xu Chen
|
| Title |
Deficiency of Autophagy-Related Gene 5 in Keratinocytes Leads to Aggravation of Epidermal Damage in 2,4-dinitrochlorobenzene-induced Allergic Contact Dermatitis
|
| Journal |
International Journal of Dermatology and Venereology
|
| Abstract |
Objective:
To determine whether keratinocyte-specific autophagy-related gene 5 (ATG5) deficiency can regulate apoptosis to inhibit skin damage in mice with 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD).
Methods:
This study involved keratinocyte-specific Atg5 conditional knockout (cKO) mice (Krt14cre/+-Atg5
flox/flox) and control mice (Krt14+/+-Atg5
flox/flox). We painted DNCB on the right ear of each mouse to induce ACD. Dermatitis scoring and measurements of ear weight and thickness were performed to evaluate inflammation levels. An immunohistochemical assay was performed to analyze immune cell infiltration. Histological study and TUNEL staining were performed to compare the differences in skin lesions between Atg5 cKO mice and control mice. Immunofluorescence and western blotting were used to examine the levels of ATG5 and apoptosis-related protein. The results were statistically analyzed by t test.
Results:
After DNCB stimulation of mice ears, we observed a more severe phenotype in Atg5 cKO mice than in control mice (dermatitis score: 7.5 ± 2.5884 vs. 3.25 ± 0.8216, P = 0.0033). Further analysis of ATG5 protein confirmed keratinocyte-specific ablation of Atg5 in cKO mice and showed that DNCB did not influence ATG5 expression. Immunohistochemistry assay revealed that the infiltrated immune cells were not involved in aggravation of the phenotype of DNCB-stimulated Atg5 cKO mice. However, the histological study (P = 0.0238), TUNEL staining (P = 0.0238), immunofluorescence (P = 0.0357), and western blotting showed that the increase in keratinocyte death, especially apoptosis, contributed to aggravation of the phenotype of DNCB-stimulated Atg5 cKO mice.
Conclusion:
Deficiency of Atg5 in keratinocytes increases apoptosis, aggravating skin damage in DNCB-induced ACD mice. This has no relationship with the involvement of immune cells.
|
| Published |
2023-3-7
|
| DOI |
10.1097/jd9.0000000000000297
|
| Resource |
| Mice |
RBRC02975 |
