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 and Yuping Lai ()
Additional contact information
Yelin Wu: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University
Yanchun Quan: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University
Yuanqi Liu: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University
Keiwei Liu: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University
Hongquan Li: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University
Ziwei Jiang: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University
Tian Zhang: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University
Hu Lei: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University
Katherine A. Radek: Burn and Shock Trauma Research Institute, Loyola University Chicago, Health Sciences Campus
Dongqing Li: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University
Zhenhua Wang: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University
Jilong Lu: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University
Wang Wang: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University
Shizhao Ji: Changhai Hospital, Second Military Medical University
Zhaofan Xia: Changhai Hospital, Second Military Medical University
Yuping Lai: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms13393 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13393

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms13393

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().