MiR-1656 targets GPX4 to trigger pyroptosis in broilers kidney tissues by activating NLRP3 inflammasome under Se deficiency

Selenium (Se) is a vital minor element for the organism. Se deficiency caused inflammation in kidney tissue and regulate the expression of selenoproteins and microRNAs (miRNAs). Pyroptosis involved in the inflammatory response, however, whether microRNA targets GPX4 to regulate Se-deficient kidney tissue pyroptosis is unclear. In this study, broilers were divided into two groups, Control group with 0.3mg/kg Se diet and Se-deficient group with 0.03mg/kg Se diet. The dual luciferase reporter assay system and quantitative real-time PCR (qRT-PCR) were used to screen the specificity of miR-1656 and its target protein in Se-deficient broilers. We tested the pyroptosis-related genes of Se-deficient broilers kidney and miR-1656-transfected primary broilers kidney by qRT-PCR, Western blot (WB) and immunofluorescence staining. Our research indicated that the GPX4 is one of the target genes of miR-1656, and Se deficiency leaded to the overexpression of miR-1656 and the increased expression of pyroptosis-related genes. The overexpression of miR-1656 can induce increased expression of pyroptosis-related genes including NLRP3, Caspase-1, IL-18, and IL-1 ,6 by inhibiting the release of GPX4. This study showed that miR-1656 could increase the release of ROS by targeting GPX4, activated the NLRP3 inflammasome, and release the inflammatory factors IL-1 ,6 and IL-18 to trigger pyroptosis in the kidney tissue of Se-deficient broilers. This finding may provide new research ideas for kidney injury and cell death due to Se deficiency.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study investigates the regulation of pyroptosis in Se-deficient broiler kidney tissue. MiR-1656 overexpression inhibits the release of GPX4, leading to increased expression of pyroptosis-related genes and triggering inflammation and cell death in the kidney tissue.