Related Experiment Video
Updated: Mar 9, 2026
Author Spotlight: Unveiling the Molecular Basis of Pain Perception and Neuropathic Pain
Published on: August 9, 2024
MiR-29c/PRKCI Regulates Axonal Growth of Dorsal Root Ganglia Neurons Under Hyperglycemia
Longfei Jia1, Lei Wang1, Michael Chopp1,2
1Department of Neurology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI, 48202, USA.
Abstract:
Diabetes initially induces distal axonal damage of peripheral nerves, but molecular mechanisms that mediate axonal injury are not fully understood. MircoRNAs (miRNAs) regulate axonal growth. We found that diabetic db/db mice exhibited substantial upregulation of miR-29c in dorsal root ganglia (DRG) neurons, sciatic nerve, and foot pad tissues. Bioinformatic analysis revealed PRKCI, a gene that encodes a member of the protein kinase C (PKC) iota, as a putative target for miR-29c. Western blot analysis showed that diabetic mice exhibited a considerable reduction of PRKCI protein levels in sciatic nerve tissues and DRG neurons. Using dual-luciferase assay, we found that co-transfection of a plasmid containing miR-29c binding site at 3' UTR of PRKCI gene and miR-29c mimics effectively reduced luminescence activity, which was abolished when miR-29c seed sequences at 3' UTR of PRKCI gene were mutated. In vitro, high glucose substantially upregulated and reduced miR-29c and PRKCI protein levels, respectively, in DRG neurons, which were associated with significant reduction of axonal growth. Knockdown of endogenous miR-29c in DRG neurons by siRNAs overcame reduced PRKCI protein and axonal growth under high glucose condition. Moreover, knockdown of PRKCI in DRG neurons by siRNAs under regular glucose condition considerably inhibited axonal growth. Together, these findings suggest that miR-29c is a negative regulator of axonal growth of DRG neurons by targeting PRKCI under hyperglycemia.
Insights
MicroRNAs (miRNAs) like miR-29c are implicated in diabetic nerve damage. High glucose increases miR-29c, reducing protein kinase C iota (PRKCI) and inhibiting axonal growth in dorsal root ganglia neurons.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Diabetes mellitus is a leading cause of peripheral neuropathy, characterized by axonal damage.
- The precise molecular mechanisms underlying diabetic axonal injury remain incompletely understood.
- MicroRNAs (miRNAs) play crucial roles in regulating axonal growth and development.
Purpose of the Study:
- To investigate the role of specific miRNAs in diabetic peripheral nerve injury.
- To identify molecular targets of dysregulated miRNAs in the context of hyperglycemia.
- To elucidate the impact of miRNA-mediated gene regulation on axonal growth in diabetic neuropathy.
Main Methods:
- Utilized diabetic db/db mouse models and in vitro high glucose cell culture systems.
- Quantified miRNA and protein expression using quantitative real-time PCR and Western blotting.
- Validated miRNA-target interactions via dual-luciferase reporter assays and siRNA-mediated gene silencing.
- Assessed axonal growth in dorsal root ganglia (DRG) neurons under various experimental conditions.
Main Results:
- Diabetic mice showed significantly increased miR-29c levels in DRG neurons, sciatic nerve, and footpad tissues.
- PRKCI (protein kinase C iota) was identified as a direct target of miR-29c.
- High glucose conditions in vitro upregulated miR-29c, decreased PRKCI protein, and inhibited axonal growth in DRG neurons.
- miR-29c knockdown restored PRKCI levels and axonal growth under high glucose; PRKCI knockdown impaired axonal growth under normal conditions.
Conclusions:
- miR-29c acts as a negative regulator of axonal growth in DRG neurons.
- Hyperglycemia-induced upregulation of miR-29c contributes to diabetic neuropathy by targeting PRKCI.
- These findings reveal a novel molecular pathway involved in diabetic axonal injury, offering potential therapeutic targets.
