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Published on: December 19, 2019
TMEM207-mediated the impairment of skin regeneration through YAP sequestration in an allergic contact dermatitis
Shusuke Nomura1, Yusuke Kito1, Chiemi Saigo1
1Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu, 501-1194, Japan.
Aim:
The Yes-associated protein (YAP) family of transcriptional coactivators has emerged as a potent promoter of cell proliferation in many types of stem/progenitor cells and cancers. Skin is a squamous epithelium that is continuously regenerated by stem/progenitor cells in the basal layer and is capable of wound healing, and YAP also plays an important role in maintaining skin homeostasis and cellular proliferation. Therefore, we focused on YAP and investigated the importance of YAP regulation in allergic contact dermatitis from the perspective of wound healing and regeneration.
Methods:
We investigated the expression and pathological characteristics of Transmembrane protein 207 (TMEM207), focusing on YAP-mediated regulation in atopic models, as abnormal TMEM207 expression may cause various functional abnormalities or regulate the function of YAP.
Results:
TMEM207 was detected not only in the stomach and large intestine but also in the bulge region of the sebaceous glands and hair roots in mice expressing TMEM207. In addition, ATP binding cassette subfamily B member 1 (ABCB1) expression decreased in the sebaceous glands, and MIB E3 Ubiquitin Protein Ligase 1 (MIB-1) expression diminished in the epidermis. Furthermore, although we were unable to confirm the binding of TMEM207 to NEDD4, we confirmed the binding of TMEM207 to the Yes1-associated transcription factor (YAP) by immunoprecipitation, and a decrease in the nuclear localization of YAP was observed by immunohistochemical staining.
Conclusion:
Our findings indicate that abnormal expression of TMEM207 is involved in the decline of skin regeneration capacity through YAP, leading to the aggravation of Allergic contact dermatitis.
Insights
Abnormal Transmembrane protein 207 (TMEM207) expression impairs skin regeneration by affecting the Yes-associated protein (YAP) pathway. This exacerbates allergic contact dermatitis, highlighting TMEM207
Area of Science:
- Dermatology and Molecular Biology
- Cellular Biology and Regenerative Medicine
Background:
- The Yes-associated protein (YAP) is crucial for cell proliferation and skin homeostasis.
- YAP plays a significant role in stem/progenitor cell function, cancer, and wound healing.
- Allergic contact dermatitis involves impaired skin regeneration.
Purpose of the Study:
- To investigate the role of Transmembrane protein 207 (TMEM207) in allergic contact dermatitis.
- To explore the YAP-mediated regulation of TMEM207 in atopic models.
- To understand how TMEM207 influences skin regeneration and disease severity.
Main Methods:
- Investigated TMEM207 expression and pathological characteristics in atopic models.
- Utilized immunoprecipitation to confirm binding between TMEM207 and YAP.
- Employed immunohistochemical staining to assess YAP nuclear localization.
Main Results:
- TMEM207 was detected in mouse sebaceous glands and hair roots.
- TMEM207 binds to YAP, and its abnormal expression leads to decreased YAP nuclear localization.
- Reduced expression of ATP binding cassette subfamily B member 1 (ABCB1) and MIB E3 Ubiquitin Protein Ligase 1 (MIB-1) was observed.
Conclusions:
- Abnormal TMEM207 expression contributes to reduced skin regeneration capacity.
- YAP dysregulation mediated by TMEM207 aggravates allergic contact dermatitis.
- TMEM207 is a potential therapeutic target for improving skin regeneration in allergic contact dermatitis.

