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

Keratinocyte-specific ablation of Mcpip1 impairs skin integrity and promotes local and systemic inflammation.
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DOI:
10.1007/s00109-019-01853-2
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发表时间:
2019-12
期刊:
Journal of molecular medicine (Berlin, Germany)
影响因子:
--
通讯作者:
Jura J
Jura J
中科院分区:
其他
文献类型:
--
作者:
Konieczny P;Lichawska-Cieslar A;Kwiecinska P;Cichy J;Pietrzycka R;Szukala W;Declercq W;Devos M;Paziewska A;Rumienczyk I;Kulecka M;Mikula M;Fu M;Borowczyk J;Santamaria-Babí LF;Jura J

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MCPIP 1(Regnase-1,由ZC 3 H12 A基因编码)调节几种炎性细胞因子的mRNA稳定性。由于这种RNA内切酶在抑制炎症中的关键作用,小鼠中Mcpip 1缺乏导致出生后多器官炎症和过早死亡的发展。在这里,我们产生了表皮中Mcpip 1条件性缺失的小鼠(Mcpip 1 EKO)。角质形成细胞中Mcpip 1的缺失导致编码与炎症和角质形成细胞分化相关的因子的转录本表达上调,如IL-36α/γ细胞因子、S100 a8/a9抗菌肽和Sprr 2d/2 h蛋白。随着年龄的增长,Mcpip 1 EKO小鼠表现出皮肤完整性受损,导致自发性皮肤病理学和全身性炎症的进行性发展。此外,我们发现表皮Mcpip 1表达的缺乏损害了角质形成细胞增殖和分化的平衡。总的来说,我们提供的证据表明,角质形成细胞特异性Mcpip 1活性对于维持皮肤完整性以及预防过度的局部和全身炎症至关重要。
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 (Mcpip1EKO). Mcpip1 loss in keratinocytes resulted in the upregulated expression of transcripts encoding factors related to inflammation and keratinocyte differentiation, such as IL-36α/γ cytokines, S100a8/a9 antibacterial peptides, and Sprr2d/2h proteins. Upon aging, the Mcpip1EKO 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.
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