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<p>Diabetic peripheral neuropathy (DPN) is a common complication of diabetes with no disease modifying treatments. Despite the prevalence, the molecular mechanisms of DPN are not fully characterized. In this study, we sought to profile microRNAs (miRNAs), key post-transcriptional regulators of gene expression, in human sural nerves with and without DPN and developed a dedicated computational pipeline (<a href="https://github.com/utdal/miRNA-Analysis">https://github.com/utdal/miRNA-Analysis</a>) for robust miRNA quantification, differential expression, and target enrichment analysis. Our analysis revealed that nearly 10% of all miRNAs detected are dysregulated and among those 74% are significantly downregulated in DPN. Target gene enrichment analysis of the differentially expressed miRNAs yielded pathways significantly associated with nerve regeneration, metabolic dysfunction, and immune cell activity. In particular, miR-21-5p is significantly upregulated in DPN, showed a positive association with axonal loss severity, and is associated with Schwann cell markers, consistent with its broader role as an injury- and inflammation-responsive miRNA that shifts from early pro-regenerative functions to maladaptive, inflammation-amplifying effects that impair Schwann cell mediated nerve repair. These results suggest that miRNAs may contribute to peripheral nerve degeneration by promoting inflammation, apoptosis, oxidative stress, and impaired nerve regeneration, while also opening potential avenues for biomarker discovery and therapeutic intervention.</p>

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Small RNA sequencing of human sural nerves identifies widespread microRNA dysregulation and Schwann cell-localized miR-21-5p in advanced diabetic neuropathy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月30日

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  • Sneha A. Gummadi,
  • Ryan R. Ju,
  • Victoria Pastor,
  • Eric C. Meyers,
  • Shai M. Rozen,
  • Diana Tavares-Ferreira

摘要

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes with no disease modifying treatments. Despite the prevalence, the molecular mechanisms of DPN are not fully characterized. In this study, we sought to profile microRNAs (miRNAs), key post-transcriptional regulators of gene expression, in human sural nerves with and without DPN and developed a dedicated computational pipeline (https://github.com/utdal/miRNA-Analysis) for robust miRNA quantification, differential expression, and target enrichment analysis. Our analysis revealed that nearly 10% of all miRNAs detected are dysregulated and among those 74% are significantly downregulated in DPN. Target gene enrichment analysis of the differentially expressed miRNAs yielded pathways significantly associated with nerve regeneration, metabolic dysfunction, and immune cell activity. In particular, miR-21-5p is significantly upregulated in DPN, showed a positive association with axonal loss severity, and is associated with Schwann cell markers, consistent with its broader role as an injury- and inflammation-responsive miRNA that shifts from early pro-regenerative functions to maladaptive, inflammation-amplifying effects that impair Schwann cell mediated nerve repair. These results suggest that miRNAs may contribute to peripheral nerve degeneration by promoting inflammation, apoptosis, oxidative stress, and impaired nerve regeneration, while also opening potential avenues for biomarker discovery and therapeutic intervention.