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Ultraviolet radiation-induced differential microRNA expression in the skin of hairless SKH1 mice, a widely used mouse model for dermatology research.

ABSTRACT: Cutaneous squamous cell carcinoma (cSCC) is the most common type of non-melanoma skin cancer that can metastasize. The major etiological factor associated with cSCC is Ultraviolet radiation (UVR) with a limited understanding of its molecular mechanism. It was hypothesized that there is a direct effect of UVR on modulation of microRNAs (miRNAs), a novel class of short noncoding RNAs which affects translation and stability of mRNAs. To test the hypothesis, the dorsal skin of the SKH1 mice (6-7 week old) was exposed to acute and chronic doses of UVR. In miRNA array profiling, we found differential expression (log fold change>1) of miR-25-5p between untreated and acute UVR treated (4kJ/m2) SKH1 mice skin. However, differential expression (>1 log fold) of miR-144-3p, miR-33-5p, miR-32-5p, miR-1983, miR-136-5p, miR-142-3p, miR-376a-3p, miR-142-5p, miR-3968, and miR-29b-3p was observed between untreated and chronically UVR treated mice skin. Differentially expressed selected miRNAs (miR-32-5p, miR-33-5p, miR-144-3p, and miR-376a-3p) were further validated in real time PCR using miRNA specific primers. Web based data mining, for the prediction of potential miRNA associated gene pathways in miRBase database revealed a link with important pathways (PI3K-Akt, MAPK, Wnt, transcriptional misregulation, and other oncogenic pathway) associated with cSCC. Furthermore, findings of PI3K-Akt pathway genes affected due to chronic UVR were confirmed using cDNA array.

SUBMITTER: Singh A

PROVIDER: S-EPMC5356709 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Ultraviolet radiation-induced differential microRNA expression in the skin of hairless SKH1 mice, a widely used mouse model for dermatology research.

Singh Ashok A Willems Estelle E Singh Anupama A Ong Irene M IM Verma Ajit K AK

Oncotarget 20161201 51

Cutaneous squamous cell carcinoma (cSCC) is the most common type of non-melanoma skin cancer that can metastasize. The major etiological factor associated with cSCC is Ultraviolet radiation (UVR) with a limited understanding of its molecular mechanism. It was hypothesized that there is a direct effect of UVR on modulation of microRNAs (miRNAs), a novel class of short noncoding RNAs which affects translation and stability of mRNAs. To test the hypothesis, the dorsal skin of the SKH1 mice (6-7 wee ...[more]

PMID: 27793049

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Project description:Workers across every occupational sector have the potential to be exposed to a wide variety of chemicals, and the skin is a primary route of exposure. Furthermore, exposure to certain chemicals has been linked to inflammatory and allergic diseases. Thus, understanding the immune responses to chemical exposures on the skin and the potential for inflammation and sensitization is needed to improve worker safety and health. Responses in the skin microenvironment impact the potential for sensitization; these responses may include proinflammatory cytokines, inflammasome activation, barrier integrity, skin microbiota, and the presence of immune cells. Selection of specific mouse strains to evaluate skin effects, such as haired (BALB/c) or hairless (SKH1) mice, varies dependent on experimental design and needs of a study. However, dermal chemical exposure may impact reactions in the skin differently depending on the strain of mouse. Additionally, there is a need for established methods to evaluate immune responses in the skin. In this study, exposure to the immunomodulatory chemical triclosan was evaluated in two mouse models using immunophenotyping by flow cytometry and gene expression analysis. BALB/c mice exposed to triclosan (2%) had a higher number and frequency of neutrophils and lower number and frequency of dendritic cells in the skin compared to controls. Although these changes were not observed in SKH1 mice, SKH1 mice exposed to triclosan had a higher number and frequency of type 2 innate lymphoid cells in the skin. Taken together, these results demonstrate that exposure to an immunomodulatory chemical, triclosan, differentially impacts immune cell populations in the skin of haired and hairless mice. Additionally, the flow cytometry panel reported in this manuscript, in combination with gene expression analysis, may be useful in future studies to better evaluate the effect of chemical exposures on the skin immune response. These findings may be important to consider during strain selection, experimental design, and result interpretation of chemical exposures on the skin.

Dataset Information

Ultraviolet radiation-induced differential microRNA expression in the skin of hairless SKH1 mice, a widely used mouse model for dermatology research.

Publications

Ultraviolet radiation-induced differential microRNA expression in the skin of hairless SKH1 mice, a widely used mouse model for dermatology research.

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