Division of Hematology and Oncology, State University of New York Downstate Health Sciences University, 450 Clarkson Avenue, MSC #20, Brooklyn, NY, 11203, USA.
Department of Chemistry, Middle Tennessee State University, Murfreesboro, TN, USA.
Ann Hematol. 2022 May;101(5):1009-1013. doi: 10.1007/s00277-022-04794-y. Epub 2022 Feb 15.
Based on previous studies showing abnormalities in the intestinal pathophysiology characterized by disruption in the gut barrier functions, and alteration in the intestinal microbial load and composition, we set out in the study to examine the expression of genes that might be involved in mediating these changes in Townes sickle cell disease (SCD) mice at 6 months old compared to non-SCD control mice. Using qPCR on total RNA isolated from the intestine, we found downregulation of the TJ genes JAM-A, Occludin, and ZO-1 in both the small intestine and colon. E-Cadherin and MUC2 were also downregulated. In contrast, gene encoding claudin-2 that mediates increase permeability to water and ions was upregulated in the small intestine. Claudin-2 upregulation is usually also associated with ongoing inflammation. Intestinal epithelium also includes Paneth cells that produce antimicrobial peptides (AMPs) that regulate intestinal microbial community. We also found that the expression of the genes encoding the AMPs defensin-α4 was reduced in the small intestine and colon and defensin-α1 in the colon in the SCD mice. Our findings are novel and provide direction for further studies into the characteristics and mechanisms of the intestinal pathophysiologic changes observed in SCD.
基于先前的研究表明，在肠道病理生理学方面存在异常，其特征是肠道屏障功能受损，肠道微生物负荷和组成发生改变，我们在这项研究中着手检查在 6 个月大的 Townes 镰状细胞病（SCD）小鼠与非 SCD 对照小鼠中可能参与介导这些变化的基因表达。我们通过从小肠和结肠分离的总 RNA 上进行 qPCR 发现，TJ 基因 JAM-A、Occludin 和 ZO-1 在小肠和结肠中均下调。E-钙黏蛋白和 MUC2 也下调。相比之下，编码 Claudin-2 的基因在小肠中上调，Claudin-2 上调通常也与持续的炎症有关。肠道上皮还包括产生调节肠道微生物群落的抗菌肽（AMPs）的潘氏细胞。我们还发现，在 SCD 小鼠的小肠和结肠中，编码 AMPs 防御素-α4 的基因表达减少，而在结肠中则减少了防御素-α1。我们的发现是新颖的，为进一步研究 SCD 中观察到的肠道病理生理变化的特征和机制提供了方向。
