PDF(Pubmed)
Abstract：
Sertoli cell -only syndrome (SCOS) is a type of testicular pathological failure that causes male infertility and no effective treatment strategy, is available for this condition. Moreover, the molecular mechanism underlying its development remains unknown. We identified DExD/H-Box helicase 58 (DDX58) as a key gene in SCOS based on four datasets of testicular tissue samples obtained from the Gene Expression Synthesis database. DDX58 was significantly upregulated in SCOS testicular Sertoli cells. Moreover, high expression of DDX58 was positively correlated with the expression of several testicular inflammatory factors, such as IL -1β, IL-18, and IL-6. Interestingly, DDX58 could be induced in the D-galactose (D-gal)-stimulated TM4 cell injury model. Whereas silencing of DDX58 inhibited D-gal -mediated p65 expression, inflammatory cytokine release, and growth arrest. Mechanistically, we found that DDX58 acts as an RNA-binding protein, which enhances p65 expression by promoting mRNA stability. Furthermore, p65 gene silencing decreased the expression of inflammatory cytokines and inhibition of cell growth in D-gal-induced cells. In conclusion, our findings demonstrate that DDX58 promotes inflammatory responses and growth arrest in SCOS Sertoli cells by stabilizing p65 mRNA. Accordingly, the DDX58/p65 regulatory axis might be a therapeutic target for SCOS.
摘要：
仅支持细胞综合征（SCOS）是导致男性不育的一种睾丸病理衰竭，没有有效的治疗策略。可用于此条件。此外，其发展的分子机制仍然未知。我们基于从基因表达合成数据库获得的睾丸组织样品的四个数据集，将DExD/H-Box解旋酶58（DDX58）鉴定为SCOS中的关键基因。DDX58在SCOS睾丸支持细胞中显著上调。此外，DDX58的高表达与几种睾丸炎症因子的表达呈正相关,如IL-1β，IL-18和IL-6。有趣的是,在D-半乳糖（D-gal）刺激的TM4细胞损伤模型中可以诱导DDX58。而DDX58的沉默抑制了D-gal介导的p65表达，炎性细胞因子释放，增长停滞。机械上,我们发现DDX58作为RNA结合蛋白，通过促进mRNA稳定性来增强p65表达。此外，p65基因沉默降低了D-gal诱导的细胞中炎症细胞因子的表达和细胞生长的抑制。总之,我们的研究结果表明,DDX58通过稳定p65mRNA促进SCOS支持细胞的炎症反应和生长停滞.因此，DDX58/p65调节轴可能是SCOS的治疗靶点.
