Abstract
Background: MicroRNAs (miRNAs) have emerged as gene expression regulators in the progression of ischemia-reperfusion injury (IRI). Accumulating evidences have indicated miR-29a play roles in myocardial and cerebral IRI. However, the role of miR-29a in testicular IRI has not been elucidated.Methods: Changes in expression of miR-29a and Transient Receptor Potential Vanilloid 4 (TRPV4) in animal samples and GC-1 spermatogenic cells were examined. The effects of miR-29a on spermatogenic cell apoptosis in testicular IRI were analyzed both in vitro and in vivo.Results: The expression of MiR-29a was negatively correlated with the expression of TRPV4 and significantly downregulated in animal samples and GC-1 cells as testicular IRI progressed. Further studies revealed TRPV4 as a downstream target of miR-29a. Inhibition of miR-29a expression increased the expression of TRPV4 and promoted spermatogenic cell apoptosis, whereas overexpression of miR-29a downregulated TRPV4 expression and suppressed spermatogenic cell apoptosis caused by testicular IRI in vitro and in vivo.Conclusion: Our results suggest that miR-29a suppresses apoptosis induced by testicular IRI by directly targeting TRPV4.
Highlights
Testicular torsion is the most common cause of urological emergency in young and adolescent males (Tuglu et al, 2016)
Enhanced Expression of Testicular Ischemia-Reperfusion InjuryTransient Receptor Potential Vanilloid 4 (TRPV4) in Testicular ischemia-reperfusion injury (IRI) Correlates with Downregulation of miR-29a Expression
To investigate if TRPV4 and miR-29a are involved in testicular IRI, we examined their expression levels in animal samples by immunohistochemistry staining, qRT-PCR and western blot
Summary
Testicular torsion is the most common cause of urological emergency in young and adolescent males (Tuglu et al, 2016). Testicular torsion/detorsion (T/D) is considered to be the primary pathophysiologic event that induces ischemia-reperfusion injury (IRI), which causes an enhancement of apoptosis and testicular spermatogenesis dysfunction (Meštrovicet al., 2014). MiR-29a and TRPV4 in Testicular Ischemia-Reperfusion Injury. TRPV4 plays a key role in regulating various cellular activities and has been found to be expressed in the kidneys, brain, lungs, skin, heart, liver, and testes (Xu et al, 2009; Wei et al, 2015; Tsuno et al, 2016). It has been reported that excessive activation of this channel is related to renal, lung, and cerebral IRI (Townsley et al, 2010; Kassmann et al, 2013; Ding et al, 2015), suggesting that TRPV4 may be an important target for mediating reperfusion injury following ischemia in many organs. MicroRNAs (miRNAs) have emerged as gene expression regulators in the progression of ischemia-reperfusion injury (IRI). The role of miR-29a in testicular IRI has not been elucidated
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