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<p>Selenium, an essential trace element, plays&#xa0;a critical role in antioxidant defence and cellular homeostasis. Selenium injection (500&#xa0;nM to 300&#xa0;µM) significantly enhanced anterior blastema regeneration in the earthworm <i>Perionyx excavatus</i>, with maximal blastema length observed at 300&#xa0;µM (4.30 ± 0.12&#xa0;mm vs. 3.09 ± 0.08&#xa0;mm in controls). Histological analysis revealed concentration-dependent tissue restoration, including longitudinal muscle layer thickness (40.9 ± 0.43&#xa0;µm at 300&#xa0;µM vs. 29.5 ± 0.38&#xa0;µm in controls) and expansion of epithelial/circular muscle layers. Quantitative PCR identified pex-miR-219 as uniquely suppressed by selenium, showing progressive downregulation (0.60-, 0.47-, 0.36-, and 0.22-fold at 1&#xa0;µM, 100&#xa0;µM, 200&#xa0;µM, and 300&#xa0;µM, respectively; p &lt; 0.001). Computational target prediction (miRanda, RNAhybrid, RNA22) and qPCR validation confirmed transcription factor Su(H) as a high-affinity target of pex-miR-219, with Su(H) mRNA upregulated 8.26-fold at 300&#xa0;µM (p &lt; 0.001). Molecular dynamics simulations demonstrated stable binding between pex-miR-219 and Su(H), evidenced by RMSD stabilization (~ 0.25&#xa0;nm after 4&#xa0;ns), low RMSF in helical regions, and persistent hydrogen bonds (30–35 bonds). These findings establish a selenium-mediated regulatory axis where suppression of pex-miR-219 relieves Su(H) repression, accelerating blastemal growth and tissue restoration. The study shows that selenium could be used as a treatment to influence miRNA pathways, which helps improve healing processes. By elucidating the pex-miR-219/Su(H) interaction, this work provides a molecular framework for developing selenium-based interventions in regenerative medicine, particularly for conditions requiring accelerated tissue repair, such as wound healing or post-traumatic regeneration. These insights could inform future strategies to harness trace elements for targeted gene regulation in human regenerative therapies.</p>

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Selenium-driven pex-miR-219 expression promotes regeneration in earthworms Perionyx excavatus

  • 期刊论文

  • 发表日期：

    2025年7月4日

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  • Ravichandran Subramaniam,
  • Johnson Retnaraj Samuel Selvan Christyraj,
  • Vyankatesh Pantam,
  • Priyadarshini Senthilkumar,
  • Jackson Durairaj Selvan Christyraj,
  • Muthukumaran Azhaguchamy,
  • Beryl Vedha Yesudhason

摘要

Selenium, an essential trace element, plays a critical role in antioxidant defence and cellular homeostasis. Selenium injection (500 nM to 300 µM) significantly enhanced anterior blastema regeneration in the earthworm Perionyx excavatus, with maximal blastema length observed at 300 µM (4.30 ± 0.12 mm vs. 3.09 ± 0.08 mm in controls). Histological analysis revealed concentration-dependent tissue restoration, including longitudinal muscle layer thickness (40.9 ± 0.43 µm at 300 µM vs. 29.5 ± 0.38 µm in controls) and expansion of epithelial/circular muscle layers. Quantitative PCR identified pex-miR-219 as uniquely suppressed by selenium, showing progressive downregulation (0.60-, 0.47-, 0.36-, and 0.22-fold at 1 µM, 100 µM, 200 µM, and 300 µM, respectively; p < 0.001). Computational target prediction (miRanda, RNAhybrid, RNA22) and qPCR validation confirmed transcription factor Su(H) as a high-affinity target of pex-miR-219, with Su(H) mRNA upregulated 8.26-fold at 300 µM (p < 0.001). Molecular dynamics simulations demonstrated stable binding between pex-miR-219 and Su(H), evidenced by RMSD stabilization (~ 0.25 nm after 4 ns), low RMSF in helical regions, and persistent hydrogen bonds (30–35 bonds). These findings establish a selenium-mediated regulatory axis where suppression of pex-miR-219 relieves Su(H) repression, accelerating blastemal growth and tissue restoration. The study shows that selenium could be used as a treatment to influence miRNA pathways, which helps improve healing processes. By elucidating the pex-miR-219/Su(H) interaction, this work provides a molecular framework for developing selenium-based interventions in regenerative medicine, particularly for conditions requiring accelerated tissue repair, such as wound healing or post-traumatic regeneration. These insights could inform future strategies to harness trace elements for targeted gene regulation in human regenerative therapies.