Suppression of LRRC19 promotes cutaneous wound healing in pressure ulcers in mice.

IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Organogenesis Pub Date : 2018-01-02 Epub Date: 2018-02-20 DOI:10.1080/15476278.2018.1436924
Jie Sun, Zhijing Wang, Xirui Wang
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引用次数: 10

Abstract

The ischemia-reperfusion (I/R) induced skin lesion has been identified as primary cause of pressure ulcer. Better understanding of the mechanism is required for new therapy development. Leucine rich repeat containing protein 19 (LRRC19) is a recently discovered transmembrane protein containing leucine-rich repeats and plays a role in immune response. To investigate the role of LRRC19 in pressure ulcers, mouse ulcer model was established with two cycles of I/R. The expression of LRRC19 was assessed during injury. siRNA mediated LRRC19 downregulation was applied to investigate the disease severity, immune cell infiltration and pro-inflammatory cytokines production. The primary skin fibroblasts were stimulated with IL-1β to dissect the molecular mechanism. LRRC19 was readily induced in I/R induced lesion site in a pattern mimicking the disease progress as measured by wound area. Knockdown of LRRC19 by siRNA significantly alleviated the disease severity and attenuated immune cell infiltration and pro-inflammatory cytokines production. In primary skin fibroblast model, siRNA knockdown of LRRC19 suppressed IL-1β mediated NFκB activation and its downstream cytokines production. LRRC19 was a novel factor for I/R-induced tissue damage by promoting NFκB dependent pro-inflammatory response. Our results supported that LRRC19 could be a potential therapeutic target for pressure ulcers.

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抑制LRRC19促进小鼠压疮皮肤创面愈合。
缺血再灌注(I/R)引起的皮肤损伤已被确定为压疮的主要原因。为了开发新的治疗方法,需要更好地了解其机制。富含亮氨酸重复序列蛋白19 (Leucine rich repeat containing protein 19, LRRC19)是最近发现的一种富含亮氨酸重复序列的跨膜蛋白,在免疫应答中起重要作用。为了研究LRRC19在压疮中的作用,我们建立了2个I/R周期的小鼠溃疡模型。损伤期间检测LRRC19的表达。应用siRNA介导的LRRC19下调研究疾病严重程度、免疫细胞浸润和促炎细胞因子的产生。用IL-1β刺激原代皮肤成纤维细胞,探讨其分子机制。LRRC19很容易在I/R诱导的病变部位被诱导,其模式模拟了通过伤口面积测量的疾病进展。siRNA敲低LRRC19可显著减轻疾病严重程度,降低免疫细胞浸润和促炎细胞因子的产生。在原代皮肤成纤维细胞模型中,siRNA敲低LRRC19可抑制IL-1β介导的NFκB活化及其下游细胞因子的产生。LRRC19是I/ r诱导的组织损伤的新因子,通过促进NFκB依赖性的促炎反应。我们的研究结果支持LRRC19可能是压疮的潜在治疗靶点。
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来源期刊
Organogenesis
Organogenesis BIOCHEMISTRY & MOLECULAR BIOLOGY-DEVELOPMENTAL BIOLOGY
CiteScore
4.10
自引率
4.30%
发文量
6
审稿时长
>12 weeks
期刊介绍: Organogenesis is a peer-reviewed journal, available in print and online, that publishes significant advances on all aspects of organ development. The journal covers organogenesis in all multi-cellular organisms and also includes research into tissue engineering, artificial organs and organ substitutes. The overriding criteria for publication in Organogenesis are originality, scientific merit and general interest. The audience of the journal consists primarily of researchers and advanced students of anatomy, developmental biology and tissue engineering. The emphasis of the journal is on experimental papers (full-length and brief communications), but it will also publish reviews, hypotheses and commentaries. The Editors encourage the submission of addenda, which are essentially auto-commentaries on significant research recently published elsewhere with additional insights, new interpretations or speculations on a relevant topic. If you have interesting data or an original hypothesis about organ development or artificial organs, please send a pre-submission inquiry to the Editor-in-Chief. You will normally receive a reply within days. All manuscripts will be subjected to peer review, and accepted manuscripts will be posted to the electronic site of the journal immediately and will appear in print at the earliest opportunity thereafter.
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