Laboratorio PABIOM, Facultad de Medicina y Ciencias Biomédicas, Universidad Autónoma de Chihuahua, Circuito Universitario Campus II, 31125, Chihuahua, Chihuahua, México.
Neuroteam CUU, Hospital Ángeles Chihuahua, Chihuahua, México.
Eur Spine J. 2023 Jun;32(6):1901-1910. doi: 10.1007/s00586-023-07721-5. Epub 2023 Apr 28.
To analyze the differential transcriptome expression in hypertrophic ligaments flavum (HLF) compared to normal ligaments.
A case-control study was conducted that included 15 patients with hypertrophy of LF and 15 controls. Samples of LF were obtained through a lumbar laminectomy and analyzed by DNA microarrays and histology. The dysregulated biological processes, signaling pathways, and pathological markers in the HLF were identified using bioinformatics tools.
The HLF had notable histological alterations, including hyalinosis, leukocyte infiltration, and disarrangement of collagen fibers. Transcriptomic analysis showed that up-regulated genes were associated with the signaling pathways of Rho GTPases, receptor tyrosine kinases (RTK), fibroblast growth factors (FGF), WNT, vascular endothelial growth factor, phosphoinositide 3-kinase (PIK3), mitogen-activated protein kinases, and immune system. The genes PIK3R1, RHOA, RPS27A, CDC42, VAV1, and FGF5, 9, 18, and 19 were highlighted as crucial markers in HLF. The down-expressed genes in the HLF had associations with the metabolism of RNA and proteins.
Our results suggest that abnormal processes in hypertrophied LF are mediated by the interaction of the Rho GTPase, RTK, and PI3K pathways, which have not been previously described in the HLF, but for which there are currently therapeutic proposals. More studies are required to confirm the therapeutic potential of the pathways and mediators described in our results.
分析与正常黄韧带相比，肥厚性黄韧带（HLF）的差异转录组表达。
进行了一项病例对照研究，共纳入 15 例 LF 肥厚患者和 15 例对照。通过腰椎椎板切除术获得 LF 样本，并通过 DNA 微阵列和组织学进行分析。使用生物信息学工具鉴定 HLF 中失调的生物过程、信号通路和病理标志物。
HLF 具有明显的组织学改变，包括玻璃样变性、白细胞浸润和胶原纤维排列紊乱。转录组分析显示，上调基因与 Rho GTPases、受体酪氨酸激酶（RTK）、成纤维细胞生长因子（FGF）、WNT、血管内皮生长因子、磷酸肌醇 3-激酶（PI3K）、丝裂原活化蛋白激酶和免疫系统的信号通路有关。PIK3R1、RHOA、RPS27A、CDC42、VAV1 和 FGF5、9、18 和 19 等基因被认为是 HLF 中的关键标志物。HLF 中下调的基因与 RNA 和蛋白质代谢有关。
我们的结果表明，肥大 LF 中的异常过程是由 Rho GTPase、RTK 和 PI3K 通路的相互作用介导的，这些通路以前在 HLF 中没有描述过，但目前有治疗建议。需要进一步研究来证实我们研究结果中描述的通路和介质的治疗潜力。
