The circ-0002538/miR-138-5p/plasmolipin axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy

Yu Tian Liu, Zhao Xu, Wei Liu, Sen Ren, He Wei Xiong, Tao Jiang, Jing Chen, Yu Kang, Qian Yun Li, Zi Han Wu, Hans Günther Machens, Xiao Fan Yang, Zhen Bing Chen

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Circular RNAs (circRNAs) play a vital role in diabetic peripheral neuropathy. However, their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood. Here, we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls. Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group. Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation. A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs. circ-0002538 was markedly downregulated in patients with diabetic peripheral neuropathy. Further in vitro experiments showed that overexpression of circ-0002538 promoted the migration of Schwann cells by upregulating plasmolipin (PLLP) expression. Moreover, overexpression of circ-0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function. The results of a mechanistic experiment showed that circ-0002538 promotes PLLP expression by sponging miR-138-5p, while a lack of circ-0002538 led to a PLLP deficiency that further suppressed Schwann cell migration. These findings suggest that the circ-0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients, improving myelin sheath structure and nerve function. Thus, this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.

Original languageEnglish
Pages (from-to)1591-1600
Number of pages10
JournalNeural Regeneration Research
Issue number7
StatePublished - Jul 2023


  • Schwann cells
  • circ-0002538
  • circRNA sequencing
  • competing endogenous RNAs
  • demyelination
  • diabetic peripheral neuropathy
  • miR-138-5
  • myelination
  • plasmolipin
  • protein profiling


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