Mechanistic insights into the connection between pollution and acne vulgaris
Acne vulgaris is a complex chronic disease that heavily impacts on the quality of life of patients. The need to elucidate the mechanisms of acne pathogenesis is driven by the growing impact in global skin disease burden and the lack of new acne therapy over decades. The comedo-switch hypothesis is b...
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| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
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Nanyang Technological University
2024
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| Online Access: | https://hdl.handle.net/10356/181283 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | Acne vulgaris is a complex chronic disease that heavily impacts on the quality of life of patients. The need to elucidate the mechanisms of acne pathogenesis is driven by the growing impact in global skin disease burden and the lack of new acne therapy over decades. The comedo-switch hypothesis is being recognized to be the key factor in driving acne as it highlights comedogenesis as the major process needed for acne development. However, the exact mechanism has yet to be elucidated. Pollutants were recently proposed to be associated with acne exacerbation, and insights unto alteration of cellular development of keratinocytes and sebocytes via aryl hydrocarbon receptor (AHR) activation suggest a possible role of AHR in acne development. Therefore, this study hypothesized that AHR signaling can initiate comedogenesis by influencing the behavior of human primary sebocyte progenitors. This is represented in a human sebaceous gland organoid (hSGO) as these recapitulate what happens during sebaceous development and growth. As demonstrated in this study, the exposure to AHR ligands, benzo[a]pyrene (B[a]P) and 2,3,7,8-tetrachlorodibenzodioxin (TCDD) can activate AHR signaling in 2D and 3D cultured sebocytes. However, pollutant exposure perturbing the development and maintenance of hSGOs was not a consequence of AHR signaling. RNAseq analysis of exposed samples revealed a change in differentiation behavior of sebocyte progenitors towards terminal differentiation of keratinocytes through the upregulation of genes involved in keratinization and cornification. This suggests that B[a]P and TCDD can drive comedo-switch in sebocyte progenitors. |
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