Btbd8 deficiency reduces susceptibility to colitis by enhancing intestinal barrier function and suppressing inflammation.

Introduction: BTBD8 has been identified as a susceptible gene for inflammatory bowel diseases (IBD). However, the function of BTBD8 in normal development and IBD pathogenesis remains unknown. Methods: We administered drinking water with 3% dextran sodium sulfate (DSS) to wild-type (WT) and Btbd8 knockout (KO) mice for seven consecutive days to induce IBD. Subsequently, we further examined whether Btbd8 KO affects intestinal barrier and inflammation. Results: We demonstrated that Btbd8 deficiency partially protects mice from DSS-induced IBD, even though no obvious phenotypes were observed in Btbd8 KO mice. Btbd8 deletion leads to strengthened tight junctions between intestinal epithelial cells, elevated intestinal stem cell activity, and enhanced mucus layer. All these three mechanisms work together to improve the intestinal barrier integrity in Btbd8 KO mice. In addition, Btbd8 deficiency mitigates inflammation by reducing the expression of IL-1ß and IL-6 by macrophages. Discussion: Our studies validate the crucial role of Btbd8 in IBD pathogenesis, and reveal that Btbd8 deficiency may ameliorate DSS-induced IBD through improving the intestinal barrier integrity, as well as suppressing inflammatory response mediated by macrophages. These findings suggest that Btbd8 could be a promising therapeutic target for the treatment of IBD.

miR-130-CYLD Axis Is Involved in the Necroptosis and Inflammation Induced by Selenium Deficiency in Pig Cerebellum.

Selenium (Se) is an essential trace element in creatures which deficiency can cause necroptosis and inflammation of multiple tissues. MicroRNAs (miRNAs) have been identified to participate multiple biological processes by regulating the expression of target genes. In the present study, the Se-deficient pig cerebellar model was established and conducted by light microscopy, qRT-PCR, and Western blot. Morphological observation exhibited necrosis-like lesions and inflammatory infiltration in the cerebellum of the Se-deficient group. Quantitative analysis result showed that Se deficiency significantly suppressed miR-130 expression, which in turn disinhibited the expression of CYLD. Meanwhile, in comparison to the control group, the expression levels of TNF-α pathway genes (TNF-α, TNFR1, and NF-κB p65) and necroptosis-related genes (RIPK1, RIPK3, and MLKL) in Se deficiency group were obviously increased (P < 0.05). Moreover, Se deficiency induced the occurrence of inflammation by upregulating the expression of inflammatory cytokines (IL-1ß, IL-2, IL-8, IL-18, IFN-γ, COX-2, PTGEs, and NLRP3). In conclusion, we proved Se deficiency could induce the deregulation of miR-130-CYLD axis to cause RIPK3-dependent necroptosis and inflammation in pig cerebellum.