Identification of a novel PPARβ/δ/miR-21-3p axis in UV-induced skin inflammation.
Identification of a novel PPARβ/δ/miR-21-3p axis in UV-induced skin inflammation.
复制标题
DOI：
10.15252/emmm.201505384
复制
发表时间：
2016-08
影响因子：
11.1
通讯作者：
Michalik L
中科院分区：
文献类型：
--
作者：
Degueurce G;D'Errico I;Pich C;Ibberson M;Schütz F;Montagner A;Sgandurra M;Mury L;Jafari P;Boda A;Meunier J;Rezzonico R;Brembilla NC;Hohl D;Kolios A;Hofbauer G;Xenarios I;Michalik L
尽管过度暴露于紫外线被广泛认为是导致皮肤紊乱和癌症的主要因素，但紫外线暴露导致的炎症性皮肤病的复杂机制仍不完全。已知核激素受体PPARβ/δ控制小鼠皮肤修复和UV诱导的皮肤癌发展。在这里，我们描述了一种新的PPARβ/δ依赖性分子级联反应，涉及TGFβ1和miR-21 - 3 p，其在表皮中响应于UV暴露而被激活。我们确定了乘客miRNA miR-21 - 3 p，我们确定为表皮中的一种新型UV诱导的miRNA，在角质形成细胞中起促炎作用，并且其在人类皮肤中的高水平表达与银屑病和鳞状细胞癌相关。最后，我们提供的证据表明，抑制miR-21 - 3 p可以减少离体人类皮肤活检中UV诱导的皮肤炎症，从而强调了基于miRNA的皮肤疾病局部治疗的临床相关性。
Although excessive exposure to UV is widely recognized as a major factor leading to skin perturbations and cancer, the complex mechanisms underlying inflammatory skin disorders resulting from UV exposure remain incompletely characterized. The nuclear hormone receptor PPARβ/δ is known to control mouse cutaneous repair and UV‐induced skin cancer development. Here, we describe a novel PPARβ/δ‐dependent molecular cascade involving TGFβ1 and miR‐21‐3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger miRNA miR‐21‐3p, that we identify as a novel UV‐induced miRNA in the epidermis, plays a pro‐inflammatory function in keratinocytes and that its high level of expression in human skin is associated with psoriasis and squamous cell carcinomas. Finally, we provide evidence that inhibition of miR‐21‐3p reduces UV‐induced cutaneous inflammation in ex vivo human skin biopsies, thereby underlining the clinical relevance of miRNA‐based topical therapies for cutaneous disorders.