| 项目编号 |
PRJCA013101 |
| 项目标题 |
Targeting the transcription factor HES1 by L-menthol restores protein phosphatase 6 in keratinocytes in models of psoriasis |
| 涉及领域 |
Medical |
| 数据类型 |
Raw sequence reads
|
| 物种名称 |
Homo sapiens
|
| 描述信息 |
Protein Phosphatase 6 down-regulation in keratinocytes is a pivotal event that amplifies the inflammatory circuits in psoriasis, indicating that restoration of PP6 can be a rational strategy for psoriasis treatment. Through the phenotypic screen, we here identify L-menthol that ameliorates psoriasis-like skin inflammation by increasing PP6 in keratinocytes. Target identification approaches reveal an indispensable role for the transcription factor hairy and enhancer of split 1 in governing the PP6-upregulating function of L-menthol in keratinocytes. HES1 is diminished in the epidermis of psoriasis patients and imiquimod-induced mouse model, while L-menthol upregulates HES1 by preventing its proteasomal degradation. Mechanistically, HES1 transcriptionally activates the expression of immunoglobulin-binding protein 1 which promotes PP6 expression and inhibits its ubiquitination. Collectively, we discover a therapeutic compound, L-menthol, for psoriasis, and uncover the dysfunctional HES1-IGBP1-PP6 axis that contributes to psoriasis pathology by using L-menthol as a probe. |
| 样品范围 |
Single cell |
| 发布日期 |
2022-11-12 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 32553276
|
|
|
|
|
| 36535970
|
Targeting the transcription factor HES1 by L-menthol restores protein phosphatase 6 in keratinocytes in models of psoriasis
|
Nature Communications
|
10.1038/s41467-022-35565-y
|
2022
|
| 40817122
|
CCR7 + dendritic cells expressing both IL-23A and IL-12B potentially contribute to psoriasis relapse
|
Nature Communications
|
10.1038/s41467-025-62874-9
|
2025
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| National Natural Science Foundation of China (NSFC)
|
|
82050009
|
|
|
|
| 提交者 |
Honglin
Wang (honglin.wang@sjtu.edu.cn)
|
| 提交单位 |
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), |
| 提交日期 |
2022-11-09 |
