Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes

Yelin Wu; Yanchun Quan; Yuanqi Liu; Keiwei Liu; Hongquan Li; Ziwei Jiang; Tian Zhang; Hu Lei; Katherine A. Radek; Dongqing Li; Zhenhua Wang; Jilong Lu; Wang Wang; Shizhao Ji; Zhaofan Xia; Yuping Lai

doi:10.1038/ncomms13393

Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes

Yelin Wu, Yanchun Quan, Yuanqi Liu, Keiwei Liu, Hongquan Li, Ziwei Jiang, Tian Zhang, Hu Lei, Katherine A. Radek, Dongqing Li, Zhenhua Wang, Jilong Lu, Wang Wang, Shizhao Ji, Zhaofan Xia, Yuping Lai

School of Life Sciences

Research output: Contribution to journal › Article › peer-review

101 Scopus citations

Abstract

Dysregulated inflammatory responses are known to impair wound healing in diabetes, but the underlying mechanisms are poorly understood. Here we show that the antimicrobial protein REG3A controls TLR3-mediated inflammation after skin injury. This control is mediated by REG3A-induced SHP-1 protein, and acts selectively on TLR3-activated JNK2. In diabetic mouse skin, hyperglycaemia inhibits the expression of IL-17-induced IL-33 via glucose glycation. The decrease in cutaneous IL-33 reduces REG3A expression in epidermal keratinocytes. The reduction in REG3A is associated with lower levels of SHP-1, which normally inhibits TLR3-induced JNK2 phosphorylation, thereby increasing inflammation in skin wounds. To our knowledge, these findings show for the first time that REG3A can modulate specific cutaneous inflammatory responses and that the decrease in cutaneous REG3A exacerbates inflammation in diabetic skin wounds.

Original language	English
Article number	13393
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms13393
State	Published - 10 Nov 2016

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title = "Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes",

abstract = "Dysregulated inflammatory responses are known to impair wound healing in diabetes, but the underlying mechanisms are poorly understood. Here we show that the antimicrobial protein REG3A controls TLR3-mediated inflammation after skin injury. This control is mediated by REG3A-induced SHP-1 protein, and acts selectively on TLR3-activated JNK2. In diabetic mouse skin, hyperglycaemia inhibits the expression of IL-17-induced IL-33 via glucose glycation. The decrease in cutaneous IL-33 reduces REG3A expression in epidermal keratinocytes. The reduction in REG3A is associated with lower levels of SHP-1, which normally inhibits TLR3-induced JNK2 phosphorylation, thereby increasing inflammation in skin wounds. To our knowledge, these findings show for the first time that REG3A can modulate specific cutaneous inflammatory responses and that the decrease in cutaneous REG3A exacerbates inflammation in diabetic skin wounds.",

author = "Yelin Wu and Yanchun Quan and Yuanqi Liu and Keiwei Liu and Hongquan Li and Ziwei Jiang and Tian Zhang and Hu Lei and Radek, \{Katherine A.\} and Dongqing Li and Zhenhua Wang and Jilong Lu and Wang Wang and Shizhao Ji and Zhaofan Xia and Yuping Lai",

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month = nov,

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doi = "10.1038/ncomms13393",

language = "英语",

volume = "7",

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T1 - Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes

AU - Wu, Yelin

AU - Quan, Yanchun

AU - Liu, Yuanqi

AU - Liu, Keiwei

AU - Li, Hongquan

AU - Jiang, Ziwei

AU - Zhang, Tian

AU - Lei, Hu

AU - Radek, Katherine A.

AU - Li, Dongqing

AU - Wang, Zhenhua

AU - Lu, Jilong

AU - Wang, Wang

AU - Ji, Shizhao

AU - Xia, Zhaofan

AU - Lai, Yuping

PY - 2016/11/10

Y1 - 2016/11/10

N2 - Dysregulated inflammatory responses are known to impair wound healing in diabetes, but the underlying mechanisms are poorly understood. Here we show that the antimicrobial protein REG3A controls TLR3-mediated inflammation after skin injury. This control is mediated by REG3A-induced SHP-1 protein, and acts selectively on TLR3-activated JNK2. In diabetic mouse skin, hyperglycaemia inhibits the expression of IL-17-induced IL-33 via glucose glycation. The decrease in cutaneous IL-33 reduces REG3A expression in epidermal keratinocytes. The reduction in REG3A is associated with lower levels of SHP-1, which normally inhibits TLR3-induced JNK2 phosphorylation, thereby increasing inflammation in skin wounds. To our knowledge, these findings show for the first time that REG3A can modulate specific cutaneous inflammatory responses and that the decrease in cutaneous REG3A exacerbates inflammation in diabetic skin wounds.

AB - Dysregulated inflammatory responses are known to impair wound healing in diabetes, but the underlying mechanisms are poorly understood. Here we show that the antimicrobial protein REG3A controls TLR3-mediated inflammation after skin injury. This control is mediated by REG3A-induced SHP-1 protein, and acts selectively on TLR3-activated JNK2. In diabetic mouse skin, hyperglycaemia inhibits the expression of IL-17-induced IL-33 via glucose glycation. The decrease in cutaneous IL-33 reduces REG3A expression in epidermal keratinocytes. The reduction in REG3A is associated with lower levels of SHP-1, which normally inhibits TLR3-induced JNK2 phosphorylation, thereby increasing inflammation in skin wounds. To our knowledge, these findings show for the first time that REG3A can modulate specific cutaneous inflammatory responses and that the decrease in cutaneous REG3A exacerbates inflammation in diabetic skin wounds.

UR - https://www.scopus.com/pages/publications/84994850942

U2 - 10.1038/ncomms13393

DO - 10.1038/ncomms13393

M3 - 文章

C2 - 27830702

AN - SCOPUS:84994850942

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 13393

ER -

Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes

Abstract

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