Keratinocyte-specific ablation of Mcpip1 impairs skin integrity and promotes local and systemic inflammation

Konieczny, Piotr; Lichawska-Cieslar, Agata; Kwiecińska, Patrycja; Cichy, Joanna; Pietrzycka, Roza; Szukała, Weronika; Declercq, Wim; Devos, Michaël; Paziewska, Agnieszka; Rumieńczyk, Izabela; Kulecka, Maria; Mikula, Michał; Fu, Mingui; Borowczyk, Julia; Santamaria‐Babí, Luis F.; Jura, Jolanta

doi:10.1007/s00109-019-01853-2

Cited by 16 publications

(23 citation statements)

References 58 publications

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“…The ZC3H12A gene is induced by many inflammatory mediators including IL-17 and IL-36 [ 19 , 20 , 21 ]. Our previous studies on the influence of MCPIP1 on keratinocytes showed that its deficiency leads to the skin barrier impairment and spontaneous cutaneous inflammation [ 22 ]. On the other hand, MCPIP1 was shown to be upregulated in human psoriatic skin [ 20 , 23 ], whereas its deficiency in mice led to the much aggravated psoriasis-like inflammation phenotype induced by imiquimod [ 21 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

MCPIP1/Regnase-1 Expression in Keratinocytes of Patients with Hidradenitis Suppurativa: Preliminary Results

Krajewski

Szukała

Lichawska-Cieslar

et al. 2021

IJMS

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The pathogenesis of hidradenitis suppurativa (HS) is yet to be fully understood. However, inflammation is a key element in the development of skin lesions. The aim of this study was to evaluate the expression of monocyte chemotactic protein-1-induced protein-1 (MCPIP1) in the skin of patients suffering from HS. Skin biopsies of 15 patients with HS and 15 healthy controls were obtained and processed for immunohistochemistry, western blot, and real time PCR. The highest mean MCPIP1 mRNA expression was found in the inflammatory lesional skin of HS patients. It was significantly higher than MCPIP1 mRNA expression in the biopsies from both healthy controls and non-lesional skin of HS patients. Western blot analysis indicated that expression of MCPIP1 was elevated within both lesional and non-lesional skin compared to the healthy control. The increased MCPIP1 mRNA and protein expression level in HS lesions may indicate its possible role in the disease pathogenesis.

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Section: Introductionmentioning

confidence: 99%

MCPIP1/Regnase-1 Expression in Keratinocytes of Patients with Hidradenitis Suppurativa: Preliminary Results

Krajewski

Szukała

Lichawska-Cieslar

et al. 2021

IJMS

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“…Regnase-1 is an IL-17-induced gene and its upregulation in psoriasis restricts IL-17 signaling and skin inflammation 29 , 30 . Keratinocyte-specific ablation of Regnase-1 promotes local and systemic inflammation partially through inhibiting the IL-36 function 44 , 45 . But unlike Regnase-1, N4BP1 mainly localizes on nucleus and thus might degrade different mRNAs and controls different biological processes.…”

Section: Discussionmentioning

confidence: 99%

The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration

Gou

et al. 2021

Cell Death Dis

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Psoriasis is a common chronic skin disease, characterized by abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells with not fully addressed molecular mechanism. N4BP1 (NEDD4-binding protein 1) is considered as an immune regulator for a long time but its physiological role is not determined yet. Here, we found that the expression of N4BP1 in skin was highest among all 54 tested tissues, and its expression was further upregulated in psoriatic skin. N4BP1-deficient mice exhibited normal grossly, but developed severe and prolonged IMQ-induced psoriasis-like disease comparing to controls. N4BP1 mainly expressed in keratinocytes and located on nucleus. Up- but not downregulated genes in N4BP1-deficient skin were specifically enriched in keratinocyte proliferation and differentiation. The proliferation of N4BP1-deficient primary keratinocytes was faster compared to that of controls. The upregulated genes upon ablation of N4BP1 were highly enriched in targets of AP-1 transcription factor. Knocking out N4BP1 resulted in upregulation of JunB and FosB, and conversely, overexpression of N4BP1 greatly reduced their expression. Furthermore, N4BP1 binds with JunB and FosB encoding mRNAs and greatly reduces their stability. In addition, with a high expression in neutrophils, N4BP1 limits survival of neutrophils in blood and infiltration of neutrophils in psoriatic skin by targeting CXCL1, CCL20, and S100A8. These findings demonstrate that N4BP1 controls the proper function of keratinocytes and neutrophils by negatively regulating JunB, FosB, and CXCL1, respectively, and that is critical for psoriasis prevention.

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“…32 Most recently, various signaling pathways involved in the epidermal development and maturation continue to be studied and still new molecular mechanisms contributing to normal and pathological barrier function are being discovered. [33][34][35][36][37] A new exciting field of investigation concerns epigenetic regulation of the homeostatic mechanisms of epidermal proliferation/ differentiation leading to the barrier formation. Involvement of the non-coding micro-RNAs and lncRNAs in stabilization of these processes through modulation of the gene transcription adds a supplementary level to the complex mechanisms of the barrier control.…”

Section: New Players In the Epidermal Barrier Functionmentioning

confidence: 99%

ARTICLE: Evolution of Skin Barrier Science for Healthy and Compromised Skin

Haftek¹,

Roy²,

Liao³

2021

JDD

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Keratinocyte-specific ablation of Mcpip1 impairs skin integrity and promotes local and systemic inflammation

Cited by 16 publications

References 58 publications

MCPIP1/Regnase-1 Expression in Keratinocytes of Patients with Hidradenitis Suppurativa: Preliminary Results

MCPIP1/Regnase-1 Expression in Keratinocytes of Patients with Hidradenitis Suppurativa: Preliminary Results

The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration

ARTICLE: Evolution of Skin Barrier Science for Healthy and Compromised Skin

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