Genes modulating intestinal permeability and microbial community are dysregulated in sickle cell disease

Autor: Maria Poplawska, Dibyendu Dutta, Manjunath Jayaram, Ngee S. Chong, Moro Salifu, Seah H. Lim
Rok vydání: 2022
Předmět:
Zdroj: Annals of Hematology. 101:1009-1013
ISSN: 1432-0584
0939-5555
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: