MCPIP3 orchestrates the balance of epidermal proliferation and differentiation

• DOI: 10.1186/s12964-025-02184-1
• Publication Date: 2025-04-08T18:19:58Z
• Authors: Agata Lichawska-C...; Weronika Szukala; Pawel Pilat; Leopold Eckhart; Jacek C Szepietowski; Jolanta Jura
• Keywords: HaCaT; Epidermis (zoology); Proinflammatory cytokine; Interleukin 20

Abstract Background Monocyte chemoattractant protein-induced protein 3 (MCPIP3), also called Regnase-3 and encoded by the ZC3H12C gene, is a member of MCPIP family RNases. Previous studies showed that MCPIP1 in keratinocytes plays pivotal role maintenance skin integrity immunological function. Given expression MCPIP3, similar to MCPIP1, increased psoriatic lesions compared with uninvolved skin, MCPIP3 regulation keratinocyte epidermal biology was hypothesized. Methods This study aimed investigate specific function skin. The pattern studied normal human (NHEKs) subjected vitro differentiation upon stimulation proinflammatory factors. Mice keratinocyte-specific deletion (Mcpip3 loxP/loxP Krt14 Cre ; EKO ) were generated characterized. response mice imiquimod (IMQ) 12-O-tetradecanoylphorbol-13-acetate (TPA) investigated. levels key modulators proliferation measured model NHEKs transiently transfected MCPIP3-specific siRNA. Reporter assays used identify direct targets nucleolytic activity. Results In keratinocytes, /MCPIP3 rapidly induced TPA, IL-17a, IL-36α, TNF-α. Although (MCPIP3 did not develop inflammation, they displayed abnormalities morphology. Stimulation IMQ TPA exacerbated hyperplasia caused deficiency led abnormal differentiation. markers, such as keratin-14, cyclin B1, involucrin, S100 calcium-binding proteins S100A7/A9, which silenced. negatively regulates level B1 mRNA via cleavage within its 3’ untranslated region. Conclusions modulates balance functions regulator morphology vivo.