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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:22

Enthalten in:

International journal of molecular sciences - 22(2021), 14 vom: 07. Juli

Sprache:

Englisch

Beteiligte Personen:

Wawro, Mateusz [VerfasserIn]
Kochan, Jakub [VerfasserIn]
Sowinska, Weronika [VerfasserIn]
Solecka, Aleksandra [VerfasserIn]
Wawro, Karolina [VerfasserIn]
Morytko, Agnieszka [VerfasserIn]
Kwiecinska, Patrycja [VerfasserIn]
Grygier, Beata [VerfasserIn]
Kwitniewski, Mateusz [VerfasserIn]
Fu, Mingui [VerfasserIn]
Cichy, Joanna [VerfasserIn]
Kasza, Aneta [VerfasserIn]

Links:

Volltext

Themen:

Cytokines
EC 3.1.-
Inflammation
Journal Article
Psoriasis
RNA, Messenger
RNases
Ribonucleases
Transcripts turnover
ZC3H12/MCPIP/Regnases
Zc3h12c protein, mouse

Anmerkungen:

Date Completed 05.08.2021

Date Revised 26.02.2024

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms22147311

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM328437972