Details

Autor(en) / Beteiligte

• Ning, Jinzhuo
• Wang, Jinrun
• Xu, Lizhe
• Li, Haoyong

Titel

MiR-153 is Involved in Testicular Ischemia/Reperfusion Injury by Directly Targeting FOXO3 and Regulating Spermatogonia Pyroptosis

Ist Teil von

• Molecular biotechnology, 2024-04

Ort / Verlag

Switzerland

Erscheinungsjahr

2024

Quelle

SpringerLink

Beschreibungen/Notizen

• IRI often occurs after detorsion of testicular torsion, which can contribute to permanent damage to sperm production function due to spermatogonia pyroptosis. Mounting data manifest that miRNAs possess a function in the IRI progression. However, the miR-153 function in testicular IRI remains unclear. We aim to elucidate the regulatory mechanism of miR-153 in regulating spermatogonia pyroptosis in testicular IRI. We developed the mouse testicular torsion/detorsion (T/D) model and the oxygen-glucose deprivation/reperfusion (OGD/R) model to examine the miR-153 function in testicular IRI. The extent of testicular ischemic damage was evaluated through HE staining the testicular tissue. Various experimental methods, including Western blotting, QRT-PCR, MDA, SOD assays, and immunohistochemistry (IHC), were deployed to examine the miR-153 levels and the generation of ROS in the testicular tissues. Furthermore, we determined the FoxO3 levels and pyroptosis-related proteins in GC-1 cells. Cell viability was assessed using the CCK-8 assay. Finally, the connection between miR-153 and FoxO3 was verified by employing dual luciferase reporter gene assays and Ago2-RIP. In the testicular IRI, we noted a significant elevation in the pyroptosis-correlated proteins NLRP3, caspase-1 (CASP1), IL-1β, and IL-18 levels. Furthermore, we noted a significant upregulation of miR-153 in the IRI testicular tissues and GC-1 cells treated with OGD/R, and the miR-153 upregulation increased cell pyroptosis. Conversely, the miR-153 downregulation and FoxO3 overexpression reduced cell pyroptosis. Subsequently, we validated that FoxO3 is a miR-153 target gene. During the OGD/R process, miR-153 increased cell pyroptosis in GC-1 cells by suppressing the FoxO3 expression. We identified that the regulation of testicular IRI-induced cell pyroptosis is mediated by miR-153 via its targeting of FoxO3.