15 Sep Mt. Sinai Researchers Explore Polycomb Induced Skin Pigmentation, Without UV Light
MedicalResearch.com Interview with:
Elena Ezhkova, PhD
Professor, Department of Cell, Developmental, and Regenerative Biology
Lab Head,The Black Family Stem Cell Institute
Icahn School of Medicine at Mount Sinai
Meng-Yen Li, PhD
The Black Family Stem Cell Institute
MedicalResearch.com: What is the background for this study?
Response: The epidermis is the primary barrier and the first line of defense to combat environmental stressors. The sun’s ultraviolet (UV) is one of the main environmental stressors that our body is exposed to daily. UV produces DNA damage in epidermal cells and is a leading cause of skin cancers.
To protect from the damaging effects of UV, epidermal cells become pigmented by melanocytes, pigment-producing cells. Taken up by epidermal cells, the melanin pigment absorbs UV light and reduces DNA damage. How the epidermis senses UV and how it leads to epidermal pigmentation is poorly understood.
MedicalResearch.com: What are the main findings? Does UV light increase the risk of both pigmented and non-pigmented skin cancers?
Response: We found that UV causes a reduction in the expression of subunits of the Polycomb complex, a key epigenetic repressor, in epidermal cells. We discovered that the reduced level of Polycomb in the epidermis leads to epidermal pigmentation — without UV exposure. We identified that the extracellular matrix protein type II collagen is a Polycomb target gene that is upregulated in UV-exposed epidermal cells. We showed that type II collagen is sufficient to drive pigmentation production in melanocytes and induce epidermal pigmentation. Altogether, our findings showed how the epidermis responds to UV and uncovered the Polycomb-type II collagen transcriptional axis in the control of epidermal pigmentation.
UV light increases the risk of both pigmented and non-pigmented skin cancers. While our current studies did not investigate the role of Polycomb or type II collagen in skin cancers, these will be the areas our future studies.
MedicalResearch.com: What should readers take away from your report?
1) We showed that UV causes epigenetic changes in epidermal cells and identified that Polycomb repression is reduced in the epidermis upon UV exposure.
2) We showed that the reduction in Polycomb in the epidermis results in epidermal pigmentation – without UV exposure. 3) We identified that type II collagen is expressed in epidermal cells upon UV exposure and that type II collagen promotes UV-induced epidermal pigmentation.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Future work is needed to uncover the molecular mechanisms by which UV exposure regulates the expression of Polycomb proteins in the epidermis.
Secondly, it will be interesting to design studies to test if type II collagen application will be advantageous to protect the epidermis from the harmful effects of UV.
Thirdly, UV treatments are currently being used to treat patients with skin hypopigmentation conditions such as vitiligo.
Our studies have shown that epidermal application of the Polycomb-specific inhibitors to the skin results in epidermal pigmentation without harmful UV exposure. Polycomb/Ezh2 inhibitors are currently being developed, with some progressing to clinical trials and an FDA approval. While the use of Polycomb-specific inhibitors for treating hypopigmentation diseases will require studies in the future, this is an interesting new avenue of investigation.
Finally, exposure to UV is a leading cause of melanoma. It is thought that a combination of factors, including genetic mutations in melanocytes, causes melanoma and but many of these factors are still unknown. Our studies show that UV-induced epigenetic changes in epidermal cells can alter the behavior of melanocytes, opening an interesting avenue of the investigation if these changes in epidermal cells interact with oncogenic mutations in melanocytes to lead to melanoma formation.
Disclosures: Dr. Jian Jin, one of the authors of this paper, received research funds from Celgene Corporation, Levo Therapeutics, and Cullgen. Dr. Jin is a cofounder, equity shareholder, and consultant of Cullgen.
Meng-Yen Li, Pooja Flora, Hong Pu, Carmit Bar, Jose Silva, Idan Cohen, Phillip M. Galbo, Hequn Liu, Xufen Yu, Jian Jin, Haruhiko Koseki, John A. D’Orazio, Deyou Zheng, Elena Ezhkova,
UV-induced reduction in Polycomb repression promotes epidermal pigmentation,
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