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Actin Cytoskeleton Affects Schwann Cell Migration and Peripheral Nerve Regeneration.

ABSTRACT: Actin cytoskeleton regulates many essential biological functions, including cellular development, shape, polarity, and motility. The organization of actin cytoskeleton has also been associated with numerous physiological and pathological conditions, for instance, the elongation of axonal growth cone during peripheral nerve regeneration. However, the spatio-temporal expression patterns of actin cytoskeleton-related genes and the specific roles of actin cytoskeleton following peripheral nerve injury have not been fully revealed. To address this question, we made rat sciatic nerve crush surgery, collected injured sciatic nerve stumps, analyzed RNA deep sequencing outcomes, and specifically studied two significantly involved canonical pathways that were related with actin, actin cytoskeleton signaling and regulation of actin-based motility by Rho. By using bioinformatic tools and qRT-PCR, We identified and validated differentially expressed genes in these two signaling pathways. Moreover, by applying actin polymerization inhibitor cytochalasin D to sciatic nerve crushed rats, we studied the in vivo effect of cytochalasin D and demonstrated that inhibiting actin polymerization would delay the migration of Schwann cells and hinder the repair and regeneration of injured peripheral nerves. Overall, our data revealed the changes of actin cytoskeleton-related genes following peripheral nerve injury and stated the importance of actin cytoskeleton during peripheral nerve regeneration.

SUBMITTER: Wang Y

PROVIDER: S-EPMC5788963 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Leukemia inhibitory factor regulates Schwann cell proliferation and migration and affects peripheral nerve regeneration.

Project description:Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that stimulates neuronal development and survival. Our previous study has demonstrated that LIF mRNA is dysregulated in the peripheral nerve segments after nerve injury. Here, we show that LIF protein is abundantly expressed in Schwann cells after rat sciatic nerve injury. Functionally, suppressed or elevated LIF increases or decreases the proliferation rate and migration ability of Schwann cells, respectively. Morphological observations demonstrate that in vivo application of siRNA against LIF after peripheral nerve injury promotes Schwann cell migration and proliferation, axon elongation, and myelin formation. Electrophysiological and behavior assessments disclose that knockdown of LIF benefits the function recovery of injured peripheral nerves. Differentially expressed LIF affects the metabolism of Schwann cells and negatively regulates ERFE (Erythroferrone). Collectively, our observations reveal the essential roles for LIF in regulating the proliferation and migration of Schwann cells and the regeneration of injured peripheral nerves, discover ERFE as a downstream effector of LIF, and extend our understanding of the molecular mechanisms underlying peripheral nerve regeneration.

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| S-EPMC7898398 | biostudies-literature

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