■骶上脊髓损伤(SSCI)后的神经源性膀胱(NB)是一种间质性疾病,伴有膀胱组织结构重塑和基质过度沉积。环状RNA(circularRNAs)通过其转录后调节功能参与纤维化疾病的发展。本研究旨在利用转录组高通量测序技术探讨SSCI后NB和膀胱纤维化的过程。
■使用T10-T11水平的脊髓横断来构建大鼠SSCI模型(10周龄雌性Wistar大鼠,重200±20g)。收集无(假手术组)和有(SSCI1-3组)NB状态的膀胱。进行形态学检查以评估膀胱纤维化的程度。此外,利用RNA测序来确定mRNA和circRNAs表达模式。进一步分析了SSCI不同时期差异表达mRNA(DEMs)和circRNAs(DECs)的动态变化。
■膀胱重量,平滑肌细胞肥大,SSCI后细胞外基质逐渐增多。与假手术组相比,3,255个DEM和1,339个DEC,3,449个DEM和1,324个DEC,884DEM,在SSCI1-3组中检测到1,151个DEC,分别。具体来说,与假手术组相比,circRNA3621,circRNA0617,circRNA0586和circRNA4426是SSCI1-3组常见的显着DECs。此外,基因本体论(GO)富集表明炎症和慢性炎症反应是SSCI后NB进展的关键事件。与“趋化因子信号通路”相关的京都基因和基因组百科全书(KEGG)通路富集,“IL-17信号通路”,和“TGF-β信号通路”表明它们可能参与调节生物过程。DECs的circRNA-miRNA-mRNA相互作用网络显示rno-circ-2239(micu2)是最大的节点,表明rno-circ-2239-miRNA-mRNA介导的网络可能在SSCI诱导的NB的发病机制中起关键作用。
■本研究对DEM和DEC在SSCI后膀胱纤维化和NB进展中的可能作用进行了全面展望。这些发现具有作为新型生物标志物和治疗靶标的潜力。
Neurogenic bladder (NB) following suprasacral spinal cord injury (SSCI) is an interstitial disease with the structural remodeling of bladder tissue and matrix over-deposition. Circular RNAs (circRNAs) are involved in fibrotic disease development through their post-transcriptional regulatory functions. This study aimed to use transcriptome high-throughput sequencing to investigate the process of NB and bladder fibrosis after SSCI.
Spinal cord transection at the T10-T11 level was used to construct the SSCI model in rats (10-week-old female Wistar rats, weighing 200 ± 20 g). The bladders were collected without (sham group) and with (SSCI 1-3 groups) NB status. Morphological examination was conducted to assess the extent of bladder fibrosis. Additionally, RNA sequencing was utilized to determine mRNAs and circRNAs expression patterns. The dynamic changes of differentially expressed mRNAs (DEMs) and circRNAs (DECs) in different periods of SSCI were further analyzed.
Bladder weight, smooth muscle cell hypertrophy, and extracellular matrix gradually increased after SSCI. Compared with the sham group, 3,255 DEMs and 1,339 DECs, 3,449 DEMs and 1,324 DECs, 884 DEMs, and 1,151 DECs were detected in the SSCI 1-3 groups, respectively. Specifically, circRNA3621, circRNA0617, circRNA0586, and circRNA4426 were significant DECs common to SSCI 1-3 groups compared with the sham group. Moreover, Gene Ontology (GO) enrichment suggested that inflammatory and chronic inflammatory responses were the key events in NB progression following SSCI. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment associated with the \"Chemokine signaling pathway\", the \"IL-17 signaling pathway\", and the \"TGF-beta signaling pathway\" suggests their potential involvement in regulating biological processes. The circRNA-miRNA-mRNA interaction networks of DECs revealed rno-circ-2239 (micu2) as the largest node, indicating that the rno-circ-2239-miRNA-mRNA-mediated network may play a critical role in the pathogenesis of SSCI-induced NB.
This study offers a comprehensive outlook on the possible roles of DEMs and DECs in bladder fibrosis and NB progression following SSCI. These findings have the potential to serve as novel biomarkers and therapeutic targets.