Deciphering the molecular landscape of human peripheral nerves: implications for diabetic peripheral neuropathy.

Autor:	Ferreira DT; Department of Neuroscience and Center for Advanced Pain Studies; University of Texas at Dallas, Richardson, TX, USA., Shen BQ; Department of Neuroscience and Center for Advanced Pain Studies; University of Texas at Dallas, Richardson, TX, USA., Mwirigi JM; Department of Neuroscience and Center for Advanced Pain Studies; University of Texas at Dallas, Richardson, TX, USA., Shiers S; Department of Neuroscience and Center for Advanced Pain Studies; University of Texas at Dallas, Richardson, TX, USA., Sankaranarayanan I; Department of Neuroscience and Center for Advanced Pain Studies; University of Texas at Dallas, Richardson, TX, USA., Kotamarti M; Department of Neuroscience and Center for Advanced Pain Studies; University of Texas at Dallas, Richardson, TX, USA., Inturi NN; Department of Neuroscience and Center for Advanced Pain Studies; University of Texas at Dallas, Richardson, TX, USA., Mazhar K; Department of Neuroscience and Center for Advanced Pain Studies; University of Texas at Dallas, Richardson, TX, USA., Ubogu EE; Department of Neurology, Division of Neuromuscular Disease, University of Alabama at Birmingham, Birmingham, AL, USA., Thomas G; Department of Orthopedic Surgery, UT Southwestern Medical Center, Dallas, Texas, USA., Lalli T; Department of Orthopedic Surgery, UT Southwestern Medical Center, Dallas, Texas, USA., Wukich D; Department of Orthopedic Surgery, UT Southwestern Medical Center, Dallas, Texas, USA., Price TJ; Department of Neuroscience and Center for Advanced Pain Studies; University of Texas at Dallas, Richardson, TX, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 16. Date of Electronic Publication: 2024 Jun 16.
DOI:	10.1101/2024.06.15.599167
Abstrakt:	Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus that is caused by metabolic toxicity to peripheral axons. We aimed to gain deep mechanistic insight into the disease process using bulk and spatial RNA sequencing on tibial and sural nerves recovered from lower leg amputations in a mostly diabetic population. First, our approach comparing mixed sensory and motor tibial and purely sensory sural nerves shows key pathway differences in affected nerves, with distinct immunological features observed in sural nerves. Second, spatial transcriptomics analysis of sural nerves reveals substantial shifts in endothelial and immune cell types associated with severe axonal loss. We also find clear evidence of neuronal gene transcript changes, like PRPH, in nerves with axonal loss suggesting perturbed RNA transport into distal sensory axons. This motivated further investigation into neuronal mRNA localization in peripheral nerve axons generating clear evidence of robust localization of mRNAs such as SCN9A and TRPV1 in human sensory axons. Our work gives new insight into the altered cellular and transcriptomic profiles in human nerves in DPN and highlights the importance of sensory axon mRNA transport as an unappreciated potential contributor to peripheral nerve degeneration. Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest.
Databáze:	MEDLINE
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