SnoN Is Involved in Regulation of the TGFβ/Smad Signaling Pathway in Patients with Degenerative Lumbar Canal Stenosis.

Degenerative lumbar canal stenosis is characterized by fibrosis-driven thickening of the ligamentum flavum, which is a key factor in the pathology of the disease and is responsible for clinical symptoms. Given the central role of transforming growth factor-β/Small mothers against decapentaplegic (Smad) signaling in fibrosis, this study aimed to investigate its role in ligamentum flavum remodeling in patients with degenerative lumbar canal stenosis. Ligamentum flavum tissue samples were obtained from 27 patients undergoing surgery for either degenerative lumbar canal stenosis (n = 18) or lumbar disc herniation (n = 9). The lumbar disc herniation patients served as the control group. The severity of the fibrosis was quantified using Masson trichrome and hematoxylin-eosin staining, and radiological measurement of ligamentum flavum thickness. Quantitative reverse transcription-polymerase chain reaction was used to analyze gene expression levels of transforming growth factor-β, transforming growth factor-β receptor, Smad2, Smad3, and Smad4. Changes at the protein level were verified using Western blot analysis. All statistical analyses were conducted post-normalization. Based on histological evaluation, the degenerative lumbar canal stenosis group showed a significantly higher degree of fibrosis compared to the control group. Radiological measurements also revealed increased ligamentum flavum thickness in the degenerative lumbar canal stenosis group (p < 0.0001). Significant upregulation (p < 0.05) of the Ski, transforming growth factor-β, transforming growth factor-β receptor, Smad2, Smad3, and Smad4 genes was detected, as confirmed by Western blot results. Collective analysis indicated that reduced SnoN gene expression in degenerative lumbar canal stenosis undermined the inhibition of target proteins on Smad2 and Smad3, resulting in elevated levels of phosphorylated Smad2/3. These findings suggest that downregulating SnoN may enhance the activation of the transforming growth factor-β/transforming growth factor-β receptor/Smad2/3 signaling pathway, thereby promoting ligamentum flavum fibrosis in patients with degenerative lumbar canal stenosis.