Department of Dermatology, University of California, San Diego, San Diego, CA, USA.
Division of Trauma, Surgical Critical Care and Burn, Department of Surgery, University of California, San Diego, San Diego, CA, USA.
Sci Adv. 2020 Mar 11;6(11):eaay0518. doi: 10.1126/sciadv.aay0518. eCollection 2020 Mar.
The complex molecular microenvironment of the wound bed regulates the duration and degree of inflammation in the wound repair process, while its dysregulation leads to impaired healing. Understanding factors controlling this response provides therapeutic targets for inflammatory disease. Esophageal cancer-related gene 4 (ECRG4) is a candidate chemokine that is highly expressed on leukocytes. We used ECRG4 knockout (KO) mice to establish that the absence of ECRG4 leads to defective neutrophil recruitment with a delay in wound healing. An in vitro human promyelocyte model identified an ECRG4-mediated suppression of the hyaluronic acid receptor, CD44, a key receptor mediating inflammation resolution. In ECRG4 KO mouse leukocytes, there was an increase in CD44 expression, consistent with a model in which ECRG4 negatively regulates CD44 levels. Therefore, we propose a previously unidentified mechanism in which ECRG4 regulates early neutrophil recruitment and subsequent CD44-mediated resolution of inflammation.
创伤床的复杂分子微环境调节着伤口修复过程中炎症的持续时间和程度，而其失调会导致愈合受损。了解控制这种反应的因素为炎症性疾病提供了治疗靶点。食管癌相关基因 4（ECRG4）是一种候选趋化因子，在白细胞上高度表达。我们使用 ECRG4 敲除（KO）小鼠来建立 ECRG4 缺失导致中性粒细胞募集缺陷和伤口愈合延迟的假说。体外人早幼粒细胞模型确定了 ECRG4 介导的透明质酸受体 CD44 的抑制作用，CD44 是介导炎症消退的关键受体。在 ECRG4 KO 小鼠的白细胞中，CD44 表达增加，这与 ECRG4 负调控 CD44 水平的模型一致。因此，我们提出了一个以前未被识别的机制，即 ECRG4 调节早期中性粒细胞募集和随后的 CD44 介导的炎症消退。
