4.5 Article

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

Journal

BIOLOGICAL TRACE ELEMENT RESEARCH
Volume 199, Issue 12, Pages 4604-4613

Publisher

SPRINGERNATURE
DOI: 10.1007/s12011-021-02612-6

Keywords

Se deficiency; CYLD; MiR-130; Necroptosis; Inflammation

Funding

  1. National Project of Students Innovative Training (SIPT) Programof Northeast Agricultural University [201910224033]

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This study revealed that selenium deficiency in pig cerebellum can induce necroptosis and inflammation by deregulating the miR-130-CYLD axis, activating the TNF-alpha pathway and necroptosis-related genes, and upregulating the expression of inflammatory cytokines.
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-alpha pathway genes (TNF-alpha, TNFR1, and NF-kappa B 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-1 beta, IL-2, IL-8, IL-18, IFN-gamma, 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.

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