Keshari Sunita, Wang Yanhan, Herr Deron Raymond, Wang Sung-Min, Yang Wu-Chang, Chuang Tsung-Hsien, Chen Chien-Lung, Huang Chun-Ming
Department of Life Sciences, National Central University, Taoyuan, 32001, Taiwan.
Department of Dermatology, University of California, San Diego, CA 92093, USA.
J Clin Med. 2020 Jan 22;9(2):312. doi: 10.3390/jcm9020312.
Pruritus and inflammation associated with accumulation of calcium phosphate (CaP) under the skin are common problems among dialysis patients with chronic kidney disease (CKD). The role of skin commensal microbiota in the CaP-induced uremic pruritus remains uncharacterized. Skin () can solubilize CaP by the production of short-chain fatty acids (SCFAs), such as butyric acid, through glucose fermentation. Like butyric acid, the N-[2-(2-Butyrylamino-ethoxy)-ethyl]-butyramide (BA-NH-NH-BA), a butyric acid derivative, remarkably induced acetylation of histone H3 lysine 9 (AcH3K9) in keratinocytes. Topical application of fermenting , butyric acid or BA-NH-NH-BA onto mouse skin effectively ameliorated CaP-induced skin itching, interleukin (IL)-6 up-regulation in keratinocytes, and extracellular signal-regulated kinase (ERK) 1/2 activation in dorsal root ganglia (DRG). Activation of ERK 1/2 by CaP was markedly reduced in IL-6 knockout mice. Genus was detected in relatively low abundance in itchy skin of patients with CKD. Our results identify a role for the skin fermenting in ameliorating CaP-induced activation of IL-6/p-ERK signaling and resulting skin inflammation. Furthermore, we provide evidence for the potential therapeutic efficacy of BA-NH-NH-BA as a postbiotic for the treatment of uremic pruritus.
与皮肤下磷酸钙（CaP）积累相关的瘙痒和炎症是慢性肾脏病（CKD）透析患者常见的问题。皮肤共生微生物群在CaP诱导的尿毒症瘙痒中的作用仍未明确。皮肤（此处原文缺失具体内容）可通过葡萄糖发酵产生短链脂肪酸（SCFAs），如丁酸，从而溶解CaP。与丁酸一样，丁酸衍生物N-[2-(2-丁酰氨基-乙氧基)-乙基]-丁酰胺（BA-NH-NH-BA）能显著诱导角质形成细胞中组蛋白H3赖氨酸9（AcH3K9）的乙酰化。将发酵的（此处原文缺失具体内容）、丁酸或BA-NH-NH-BA局部应用于小鼠皮肤，可有效改善CaP诱导的皮肤瘙痒、角质形成细胞中白细胞介素（IL）-6的上调以及背根神经节（DRG）中细胞外信号调节激酶（ERK）1/2的激活。在IL-6基因敲除小鼠中，CaP对ERK 1/2的激活明显降低。在CKD患者的瘙痒皮肤中检测到（此处原文缺失具体内容）属的丰度相对较低。我们的研究结果确定了皮肤发酵（此处原文缺失具体内容）在改善CaP诱导的IL-6/p-ERK信号激活及由此导致的皮肤炎症中的作用。此外，我们提供了证据表明BA-NH-NH-BA作为一种后生元在治疗尿毒症瘙痒方面具有潜在的治疗效果。
