Department of Biological Sciences, Cellular Heterogeneity Research Center, Sookmyung Women's University, Seoul 04310, Korea.
Research Institute of Women's Health, Sookmyung Women's University, Seoul 04310; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.
BMB Rep. 2020 Jul;53(7):385-390. doi: 10.5483/BMBRep.2020.53.7.298.
Inflammatory Bowel Disease is caused by an acute or chronic dysfunction of the mucosal inflammatory system in the intestinal tract. In line with the results of our previous study, wherein we found that the PKCα-LSD1-NF-κB signaling plays a critical role in the prolonged activation of the inflammatory response, we aimed to investigate the effect of signaling on colitis in the present study. Lsd1 S112A knock-in (Lsd1SA/SA) mice, harboring a deficiency in phosphorylation by PKCα, exhibited less severe colitis symptoms and a relatively intact colonic epithelial lining in dextran sulfate sodium (DSS)- induced colitis models. Additionally, a reduction in pro-inflammatory gene expression and immune cell recruitment into damaged colon tissues in Lsd1SA/SA mice was observed upon DSS administration. Furthermore, LSD1 inhibition alleviated colitis symptoms and reduced colonic inflammatory responses. Both LSD1 phosphorylation and its activity jointly play a role in the progression of DSS-induced colitis. Therefore, the inhibition of LSD1 activity could potentially protect against the colonic inflammatory response. [BMB Reports 2020; 53(7): 385-390].
炎症性肠病是由肠道黏膜炎症系统的急性或慢性功能障碍引起的。与我们之前的研究结果一致，即我们发现 PKCα-LSD1-NF-κB 信号通路在炎症反应的持续激活中起着关键作用，本研究旨在研究该信号通路对结肠炎的影响。Lsd1 S112A 敲入（Lsd1SA/SA）小鼠中，PKCα 磷酸化缺陷，在葡聚糖硫酸钠（DSS）诱导的结肠炎模型中表现出较轻的结肠炎症状和相对完整的结肠上皮衬里。此外，在给予 DSS 后，Lsd1SA/SA 小鼠的促炎基因表达减少，免疫细胞募集到受损的结肠组织中。此外，LSD1 抑制减轻了结肠炎症状并降低了结肠炎症反应。LSD1 的磷酸化及其活性共同参与了 DSS 诱导的结肠炎的进展。因此，抑制 LSD1 活性可能有助于防止结肠炎症反应。[BMB 报告 2020；53(7): 385-390]。
