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Stimulation of melanin synthesis by UVB is mediated by NO/cGMP/PKG cascade targeting PAK4 in vitro

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Abstract

The coat color of mammals is primarily determined by the type, quantity, and distribution of melanin in the skin and hair. As an endogenous gas molecule, nitric oxide (NO) regulates tyrosinase production by modulating the cGMP-dependent protein kinase (PKG) pathway, which enhances melanin synthesis. However, some interrelationships have not been fully elucidated. In the present study, mouse melanocytes co-cultured with mouse keratinocytes in vitro, or as monocultures, were used as research models. The results indicated that ultraviolet B irradiation increased nitric oxide synthase (NOS) activity and NO production, and increased PKG, p21-activated kinase 4 (PAK4), and microphthalmia-associated transcription factor (MITF) levels, as well as tyrosinase (TYR), tyrosinase-related protein 1 and 2 expression, and melanin synthesis. During PKG inhibition, the expression of NO-regulated PAK4 and MITF was decreased. Pigment production was also affected, but remained higher than that in the control and NO inhibitor groups. These findings suggest that ultraviolet light regulates melanin production by activating the NO/cGMP/PKG pathway, which mediates the expression of PAK4, affecting melanin synthesis. On this basis, further elucidation of this regulatory network may improve our understanding of patterns of animal hair color formation.

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Acknowledgements

We are grateful to Haidong Wang for the editing and critical reading of the manuscript. The authors thank Xiaomao Luo and Xiuju Yu for the valuable, scientific, and technical support of the project.

Funding

The present study was sponsored by the National Natural Science Foundation of China (grant no. 31772690) and Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province and the National Natural Science of Shanxi Province (grant no. 201701D121106).

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Authors and Affiliations

  1. College of Veterinary Medicine, Shanxi Agricultural University, No. 1 Mingxian South Road, Jinzhong, Shanxi, 030801, People’s Republic of China

    Linli Xue, Lucheng Chang, Yilei Li & Xiaoyan He

  2. College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People’s Republic of China

    Yanjun Dong

Authors
  1. Linli Xue
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  2. Lucheng Chang
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  3. Yilei Li
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  4. Yanjun Dong
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  5. Xiaoyan He
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Contributions

XH designed the study. LX, LC, and YL conducted the studies and participated in data collection. YD performed the statistical analysis and assisted in the study design. LX performed statistical analysis and drafted the manuscript. All authors read and approved the final manuscript.

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Correspondence to Xiaoyan He.

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The authors declare no competing interests.

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Editor: Tetsuji Okamoto

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Xue, L., Chang, L., Li, Y. et al. Stimulation of melanin synthesis by UVB is mediated by NO/cGMP/PKG cascade targeting PAK4 in vitro. In Vitro Cell.Dev.Biol.-Animal 57, 280–289 (2021). https://doi.org/10.1007/s11626-021-00551-z

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  • DOI: https://doi.org/10.1007/s11626-021-00551-z

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