Overexpression and potential roles of NRIP1 in psoriasis

Abstract

Nuclear receptor interacting protein 1 (NRIP1, also known as RIP140) is a co-regulator for various transcriptional factors and nuclear receptors, and has been shown to take part in many biological and pathological processes, such as regulating mammary gland development and inflammatory response.The aim of this study is to investigate the expression of NRIP1 and to explore its roles in the pathogenesis of psoriasis. Thirty active psoriasis patients and 16 healthy volunteers were enrolled for this study. qRT-PCR analyses found that both NRIP1 and RelA/p65 were elevated in psoriatic lesions compared to psoriatic non-lesions and normal controls, and also overexpressed in peripheral blood mononuclear cell (PBMCs) of psoriasis patients. Suppression of NRIP1 in HaCaT cells could significantly inhibit cell growth and induce apoptosis, and the suppression of NRIP1 in CD4+ T cells isolated from psoriasis patients could downregulate the expression of RelA/p65 and decrease the secretion of IL-17. Furthermore, in Nrip1 knockout mice, IMQ-induced inflammation of skin was delayed and the RelA/p65 expression in lesions was reduced. In conclusion, our data suggests that NRIP1 is overexpressed both in skin and PBMCs of psoriasis patients and may be involved in the abnormal proliferation and apoptosis of keratinocytes, as well as the immune reaction through the regulation of RelA/p65. Therefore, NRIP1 may be a potential therapeutic target for psoriasis.

Potentiation of Psoriasis-Like Inflammation by PCSK9

“…Psoriasis and these comorbidities share a number of same inflammatory cytokines, such as Th1 and Th17 inflammatory molecules, which promote a proinflammatory state . The combination of our previous studies in metabolism and psoriasis have resulted in the identification of a psoriasis gene, NRIP1 (Luan et al, 2016). This study showed another candidate gene, PCSK9, which plays an important role in metabolism and has the potential to be a therapeutic target for treatment of psoriasis.…”

Metabolic Syndrome and Skin Diseases

“…In psoriasis, numerous effector cells including keratinocytes, Th17 cells, and dendritic cells activated by TNF-α, plasmin and TLRs could produce cytokines and chemokines via the NFκB pathway, which leads to psoriatic phenotypes (140). Moreover, our recent studies reported that metabolic-associated genes PCSK9 and nuclear receptor interacting protein 1 (NRIP1) both play important roles in psoriasis via the NFκB pathway (115, 141). It has been reported that PCSK9 silencing can suppress atherosclerosis by inhibiting the TLR4/NFκB signaling pathway (142).…”

“…NFκB (RelA) can inversely resolute the inflammatory response by targeting and degrading NRIP1 via recruiting the SCF (Skp, culin, F-box-containing) E3 ligase complex (145). Our laboratory revealed that suppression of NRIP1 in CD4+ T cells that were isolated from psoriasis patients could downregulate the expression of RelA/p65 and decrease the secretion of IL-17, thus inhibiting the inflammation in psoriasis (141). Importantly, together, PCSK9 and NRIP1 may be two potential therapeutic targets for both psoriasis and metabolic syndrome by regulating the NFκB-associated chronic inflammatory status.…”

Advances in Understanding the Immunological Pathways in Psoriasis

“…Moreover, animal studies showed that imiquimod-induced inflammation was delayed in knockout NRIP1 mice. The authors suggested that NRIP1 could induce abnormal proliferation and apoptosis of keratinocytes through direct interaction with Re1A/p65 [106].…”