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

被引：16

作者：

Konieczny, Piotr ^{[1
]}

Lichawska-Cieslar, Agata ^{[1
]}

Kwiecinska, Patrycja ^{[2
]}

Cichy, Joanna ^{[2
]}

Pietrzycka, Roza ^{[1
]}

Szukala, Weronika ^{[1
]}

Declercq, Wim ^{[3
,4
]}

Devos, Michael ^{[3
,4
]}

Paziewska, Agnieszka ^{[5
]}

Rumienczyk, Izabela ^{[5
]}

Kulecka, Maria ^{[5
]}

Mikula, Michal ^{[6
]}

Fu, Mingui ^{[7
,8
]}

Borowczyk, Julia ^{[9
,10
]}

Santamaria-Babi, Luis F. ^{[11
]}

Jura, Jolanta ^{[1
]}

机构：

[1] Jagiellonian Univ, Dept Gen Biochem, Fac Biochem Biophys & Biotechnol, Gronostajowa 7, PL-30387 Krakow, Poland

[2] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Immunol, Gronostajowa 7, PL-30387 Krakow, Poland

[3] VIB Ctr Inflammat Res Ctr, Mol Signaling & Cell Death Unit, Ghent, Belgium

[4] Univ Ghent, Dept Biomed Mol Biol, Technol Pk 71, B-9052 Ghent, Belgium

[5] Med Ctr Postgrad Educ, Dept Gastroenterol Hepatol & Clin Oncol, Marymoncka 99-103, PL-01813 Warsaw, Poland

[6] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Genet, Roentgena 5, PL-02781 Warsaw, Poland

[7] Univ Missouri Kansas City, Dept Biomed Sci, Sch Med, 5100 Rockhill Rd, Kansas City, MO 64110 USA

[8] Univ Missouri Kansas City, Shock Trauma Res Ctr, Sch Med, 5100 Rockhill Rd, Kansas City, MO 64110 USA

[9] Jagiellonian Univ, Dept Cell Biol, Fac Biochem Biophys & Biotechnol, Gronostajowa 7, PL-30387 Krakow, Poland

[10] Univ Geneva, Dept Pathol & Immunol, Fac Med, Rue Gabrielle Perret Gentil 4, CH-1211 Geneva, Switzerland

[11] Univ Barcelona, Fac Biol, Dept Cellular Biol Physiol & Immunol, Translat Immunol, Gran Via Corts Catalanes 585, Barcelona 08007, Spain

来源：

JOURNAL OF MOLECULAR MEDICINE-JMM | 2019年 / 97卷 / 12期

关键词：

MCPIP1; Regnase-1; Skin inflammation; BARRIER FUNCTION; MOUSE MODEL; DISEASE; PROTEIN; DEGRADATION; EXPRESSION; EPIDERMIS; CLEAVAGE; RNASE; DIFFERENTIATION;

D O I：

10.1007/s00109-019-01853-2

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

MCPIP1 (Regnase-1, encoded by the ZC3H12A gene) regulates the mRNA stability of several inflammatory cytokines. Due to the critical role of this RNA endonuclease in the suppression of inflammation, Mcpip1 deficiency in mice leads to the development of postnatal multiorgan inflammation and premature death. Here, we generated mice with conditional deletion of Mcpip1 in the epidermis (Mcpip1(EKO)). Mcpip1 loss in keratinocytes resulted in the upregulated expression of transcripts encoding factors related to inflammation and keratinocyte differentiation, such as IL-36 alpha/gamma cytokines, S100a8/a9 antibacterial peptides, and Sprr2d/2h proteins. Upon aging, the Mcpip1(EKO) mice showed impaired skin integrity that led to the progressive development of spontaneous skin pathology and systemic inflammation. Furthermore, we found that the lack of epidermal Mcpip1 expression impaired the balance of keratinocyte proliferation and differentiation. Overall, we provide evidence that keratinocyte-specific Mcpip1 activity is crucial for the maintenance of skin integrity as well as for the prevention of excessive local and systemic inflammation. Key messages Loss of murine epidermal Mcpip1 upregulates transcripts related to inflammation and keratinocyte differentiation. Keratinocyte Mcpip1 function is essential to maintain the integrity of skin in adult mice. Ablation of Mcpip1 in mouse epidermis leads to the development of local and systemic inflammation.

引用

页码：1669 / 1684

页数：16

共 59 条

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