title: The HMGB1 signaling pathway activates the inflammatory response in Schwann cells.
abstract: Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an inflammatory response in Schwann cells. However, it is unclear whether specific endogenous damage-associated molecular pattern molecules are involved in the inflammatory response following nerve injury. In the present study, we demonstrate that a key damage-associated molecular pattern molecule, high mobility group box 1 (HMGB1), is upregulated following rat sciatic nerve axotomy, and we show colocalization of the protein with Schw-ann cells. HMGB1 alone could not enhance expression of Toll-like receptors or the receptor for advanced glycation end products (RAGE), but was able to facilitate migration of Schwann cells. When Schwann cells were treated with HMGB1 together with lipopolysaccharide, the expression levels of Toll-like receptors and RAGE, as well as inflammatory cytokines were upregulated. Our novel findings demonstrate that the HMGB1 pathway activates the inflammatory response in Schwann cells following peripheral nerve injury.
authors.affiliation: Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Li-Li
authors.identifier: 0000-0001-5040-8926
authors.initials: LL
authors.lastname: Man
authors.affiliation: Department of Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.affiliation: Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Hong-Hua
authors.initials: HH
authors.lastname: Song
authors.affiliation: Medical College, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Xu
authors.affiliation: Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Zi-Wen
authors.initials: ZW
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Wang
keywords: DAMPs; HMGB1; Schwann cells; TLRs; cytokines; inflammatory response; migration; nerve regeneration; neural regeneration; peripheral nerve injury; peripheral nerves; sciatic nerve transection