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

Abstract

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.

Therapeutic effect of paeoniflorin on chronic constriction injury of the sciatic nerve via the inhibition of Schwann cell apoptosis

“…The proliferation and migration of Schwann cells in rats after sciatic nerve injury enabled nerve regeneration and substantial functional recovery (Q. Chen, Liu, Zhang, Li, & Yi, 2021). Schwann cells are a dominant glial cell type in the neural system and can promote axonal regeneration (Gonzalez-Perez et al, 2018).…”

Research Hotspots and Trends of Peripheral Nerve Injuries Based on Web of Science From 2017 to 2021: A Bibliometric Analysis

“…It can be observed that the group with Yi Sheng as the core was large, and there was more cooperation within the group. Yi Sheng worked at Nantong University, China, where he focused on microRNA ( 38 , 39 ), and Schwann cells ( 40 , 41 ). Notably, most of the authors in this group were from East Asia, and there was less collaboration with authors from Europe.…”

Plasma Cytokine Profiles in Patients With Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration

“…LIF is a member of the IL-6 family of cytokines, expressed during inflammation. It has been reported to upregulate in response to different types of retinal diseases and possess various pharmacological effects, including promoting and inhibiting retinal vascular development, protecting the integrity of the vasculature, preventing retinal injury, and displaying neuroprotective properties 23–25. There were few studies on the levels of LIF in PCV and nAMD.…”