Halasi Marianna, Grinstein Mor, Adini Avner, Adini Irit
Department of Surgery, Center for Engineering in Medicine & Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Medicine, Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
J Inflamm Res. 2022 Aug 8;15:4515-4526. doi: 10.2147/JIR.S366290. eCollection 2022.
Epidemiological studies have associated pigment production with protection against certain human diseases. In contrast to African Americans, European descendants are more likely to suffer from angiogenesis-dependent and inflammatory diseases, such as wet age-related macular degeneration (ARMD) and ulcerative colitis (UC), respectively.
In a mouse model of dextran sulfate sodium (DSS)-induced acute colitis, the effect of fibromodulin (FMOD) depletion was examined on colitis severity.
In this study, albino mice that produce high levels of FMOD developed less severe acute colitis compared with mice lacking in FMOD as assessed by clinical symptoms and histopathological changes. FMOD depletion affected the expression of tight junction proteins, contributing to the destruction of the epithelial barrier. Furthermore, this study revealed a stronger inflammatory response after DSS treatment in the absence of FMOD, where FMOD depletion led to an increase in activated T cells, plasmacytoid dendritic cells (pDCs), and type I interferon (IFN) production.
These findings point to FMOD as a potential biomarker of disease severity in UC among light-skinned individuals of European descent.
流行病学研究已将色素生成与预防某些人类疾病联系起来。与非裔美国人相比，欧洲后裔分别更易患血管生成依赖性疾病和炎症性疾病，如湿性年龄相关性黄斑变性（ARMD）和溃疡性结肠炎（UC）。
在葡聚糖硫酸钠（DSS）诱导的急性结肠炎小鼠模型中，研究了纤维调节蛋白（FMOD）缺失对结肠炎严重程度的影响。
在本研究中，通过临床症状和组织病理学变化评估，与缺乏FMOD的小鼠相比，产生高水平FMOD的白化病小鼠发生的急性结肠炎较轻。FMOD缺失影响紧密连接蛋白的表达，导致上皮屏障破坏。此外，本研究显示在缺乏FMOD的情况下，DSS处理后炎症反应更强，其中FMOD缺失导致活化T细胞、浆细胞样树突状细胞（pDC）增加以及I型干扰素（IFN）产生增加。
这些发现表明，FMOD是欧洲血统浅肤色个体中UC疾病严重程度的潜在生物标志物。
