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Article

Molecular Mechanisms of ZC3H12C/Reg-3 Biological Activity and Its Involvement in Psoriasis Pathology

by
Mateusz Wawro
1,
Jakub Kochan
1,
Weronika Sowinska
1,
Aleksandra Solecka
1,
Karolina Wawro
1,
Agnieszka Morytko
2,
Patrycja Kwiecinska
2,
Beata Grygier
2,
Mateusz Kwitniewski
2,
Mingui Fu
3,
Joanna Cichy
2 and
Aneta Kasza
1,*
1
Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland
2
Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland
3
Department of Biomedical Science and Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(14), 7311; https://doi.org/10.3390/ijms22147311
Submission received: 14 May 2021 / Revised: 22 June 2021 / Accepted: 2 July 2021 / Published: 7 July 2021
(This article belongs to the Special Issue Mechanisms of Innate Immune Activation and Regulation in Health and Disease)
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Abstract

The members of the ZC3H12/MCPIP/Regnase family of RNases have emerged as important regulators of inflammation. In contrast to Regnase-1, -2 and -4, a thorough characterization of Regnase-3 (Reg-3) has not yet been explored. Here we demonstrate that Reg-3 differs from other family members in terms of NYN/PIN domain features, cellular localization pattern and substrate specificity. Together with Reg-1, the most comprehensively characterized family member, Reg-3 shared IL-6, IER-3 and Reg-1 mRNAs, but not IL-1β mRNA, as substrates. In addition, Reg-3 was found to be the only family member which regulates transcript levels of TNF, a cytokine implicated in chronic inflammatory diseases including psoriasis. Previous meta-analysis of genome-wide association studies revealed Reg-3 to be among new psoriasis susceptibility loci. Here we demonstrate that Reg-3 transcript levels are increased in psoriasis patient skin tissue and in an experimental model of psoriasis, supporting the immunomodulatory role of Reg-3 in psoriasis, possibly through degradation of mRNA for TNF and other factors such as Reg-1. On the other hand, Reg-1 was found to destabilize Reg-3 transcripts, suggesting reciprocal regulation between Reg-3 and Reg-1 in the skin. We found that either Reg-1 or Reg-3 were expressed in human keratinocytes in vitro. However, in contrast to robustly upregulated Reg-1 mRNA levels, Reg-3 expression was not affected in the epidermis of psoriasis patients. Taken together, these data suggest that epidermal levels of Reg-3 are negatively regulated by Reg-1 in psoriasis, and that Reg-1 and Reg-3 are both involved in psoriasis pathophysiology through controlling, at least in part different transcripts.
Keywords: ZC3H12/MCPIP/Regnases; transcripts turnover; RNases; inflammation; psoriasis ZC3H12/MCPIP/Regnases; transcripts turnover; RNases; inflammation; psoriasis

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MDPI and ACS Style

Wawro, M.; Kochan, J.; Sowinska, W.; Solecka, A.; Wawro, K.; Morytko, A.; Kwiecinska, P.; Grygier, B.; Kwitniewski, M.; Fu, M.; et al. Molecular Mechanisms of ZC3H12C/Reg-3 Biological Activity and Its Involvement in Psoriasis Pathology. Int. J. Mol. Sci. 2021, 22, 7311. https://doi.org/10.3390/ijms22147311

AMA Style

Wawro M, Kochan J, Sowinska W, Solecka A, Wawro K, Morytko A, Kwiecinska P, Grygier B, Kwitniewski M, Fu M, et al. Molecular Mechanisms of ZC3H12C/Reg-3 Biological Activity and Its Involvement in Psoriasis Pathology. International Journal of Molecular Sciences. 2021; 22(14):7311. https://doi.org/10.3390/ijms22147311

Chicago/Turabian Style

Wawro, Mateusz, Jakub Kochan, Weronika Sowinska, Aleksandra Solecka, Karolina Wawro, Agnieszka Morytko, Patrycja Kwiecinska, Beata Grygier, Mateusz Kwitniewski, Mingui Fu, and et al. 2021. "Molecular Mechanisms of ZC3H12C/Reg-3 Biological Activity and Its Involvement in Psoriasis Pathology" International Journal of Molecular Sciences 22, no. 14: 7311. https://doi.org/10.3390/ijms22147311

APA Style

Wawro, M., Kochan, J., Sowinska, W., Solecka, A., Wawro, K., Morytko, A., Kwiecinska, P., Grygier, B., Kwitniewski, M., Fu, M., Cichy, J., & Kasza, A. (2021). Molecular Mechanisms of ZC3H12C/Reg-3 Biological Activity and Its Involvement in Psoriasis Pathology. International Journal of Molecular Sciences, 22(14), 7311. https://doi.org/10.3390/ijms22147311

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