Article
Immunology
Amanda Brosius Lutz, Tawaun A. Lucas, Glenn A. Carson, Christine Caneda, Lu Zhou, Ben A. Barres, Marion S. Buckwalter, Steven A. Sloan
Summary: The response of Schwann cells to peripheral nerve injury involves the modulation of specific cellular pathways, including the downregulation of the AGE/RAGE pathway and secreted molecules Sparcl1 and Sema5a. These findings contribute to our understanding of neuroinflammation and provide valuable insights for improving CNS regeneration.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Cell Biology
Lixia Li, Yizhou Xu, Xianghai Wang, Jingmin Liu, Xiaofang Hu, Dandan Tan, Zhenlin Li, Jiasong Guo
Summary: Ascorbic acid accelerates Wallerian degeneration by promoting the degradation of axons and myelin in injured nerves, inducing Schwann cell dedifferentiation, and enhancing macrophage recruitment and phagocytosis.
NEURAL REGENERATION RESEARCH
(2021)
Article
Immunology
Eri Oshima, Yoshinori Hayashi, Zhen Xie, Hitoshi Sato, Suzuro Hitomi, Ikuko Shibuta, Kentaro Urata, Junjun Ni, Koichi Iwata, Tatsuo Shirota, Masamichi Shinoda
Summary: This study aimed to identify the axon regeneration factor derived from M2 macrophages. Transcriptome analysis revealed the upregulation of the macrophage-selective lysosomal protease CTSS in the injured nerve. Macrophage ablation experiments in a rat model showed that ablation at the injured site hindered partial recovery from sensory deficits. CTSS was upregulated in the injured nerve and facilitated endogenous recovery from hypoesthesia. Additionally, CTSS promoted axon regeneration by activating Schwann cells through Ephrin-B2 shedding from fibroblasts.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Neurosciences
Yunsong Zhang, Yinying Shen, Li Zhao, Qian Zhao, Lili Zhao, Sheng Yi
Summary: Nerve injury-induced Schwann cell dedifferentiation promotes axon growth by creating a favorable microenvironment. Transcription factor BCL11A plays a crucial role in Schwann cell reprogramming during peripheral nerve regeneration. Silencing Bcl11a reduces Schwann cell viability, proliferation, migration rates, and debris clearance ability. Bcl11a deficiency leads to restricted axon elongation and myelin wrapping, resulting in failed recovery. Mechanistically, BCL11A regulates Schwann cell activity by binding to the Nr2f2 promoter and modulating Nr2f2 expression. In conclusion, BCL11A is essential for Schwann cell activation and peripheral nerve regeneration, making it a potential therapeutic target for peripheral nerve injury treatment.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Jun Sun, Zhi Liao, Zhangyu Li, Hao Li, Zhimin Wu, Chuan Chen, Hui Wang
Summary: This study focused on investigating the roles and mechanisms of exosomes derived from Schwann cells under different conditions in regulating macrophagic sub-phenotypes and peripheral nerve injury repair. The study found that exosomes from normal oxygen condition Schwann cells promoted M2 macrophagic polarization and facilitated axon elongation, while exosomes from post-injury oxygen-glucose-deprivation-condition Schwann cells promoted M1 polarization and inhibited axon elongation. The down-regulation of miR-146a-5p was closely related to the shift of exosomes to pro-inflammatory phenotype. The study concluded that miR-146a-5p played an important role in regulating macrophagic phenotype and had implications for axonal regeneration and functional recovery.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yaxian Wang, Fuchao Zhang, Yunsong Zhang, Qi Shan, Wei Liu, Fengyuan Zhang, Feiyu Zhang, Sheng Yi
Summary: Research findings indicate that Btc plays essential roles in regulating Schwann cell migration and axon elongation, suggesting the potential application of Btc as a regenerative strategy for treating peripheral nerve injury.
MOLECULAR MEDICINE
(2021)
Review
Biotechnology & Applied Microbiology
Jue Ling, Chang He, Shuxuan Zhang, Yahong Zhao, Meifeng Zhu, Xiaoxuan Tang, Qiaoyuan Li, Liming Xu, Yumin Yang
Summary: This article provides an overview of evaluation methods used to study scaffold-based therapies for peripheral nerve injury (PNI) in experimental animal models, with particular focus on Schwann cell functions and axonal growth within the regenerated nerve.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Review
Neurosciences
Zhiqian Ye, Junbin Wei, Chaoning Zhan, Jin Hou
Summary: Peripheral nerve injury is a common concern in trauma patients, and the outcome of repair surgeries can be unsatisfactory. Transforming growth factor-beta (TGF-beta), a multifunctional cytokine, plays a crucial role in peripheral nerve regeneration by enhancing nerve regrowth capacity. The potential of TGF-beta in promoting nerve regeneration is promising, providing new cues for better treatment of peripheral nerve injuries.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Neurosciences
Estefania Contreras, Sara Bolivar, Xavier Navarro, Esther Udina
Summary: Neurons in the peripheral nervous system have the ability to regenerate their axons after injury by triggering a complex activation response. Schwann cells (SCs) play an active role in regulating axonal programs and orchestrating Wallerian degeneration and axonal regeneration through both cell-to-cell contacts and secreted signals. The secretome, which includes proteins, cytokines, growth factors, and extracellular vesicles, facilitates communication and is essential for axonal regeneration. The use of secretome has emerged as a promising alternative to cell therapy, reducing the risks associated with cell use. In this review, the roles of SC and macrophage secretomes in peripheral nerve injury are discussed, along with the use of secretomes in experimental models to enhance nerve regeneration.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Neurosciences
Panjian Lu, Gang Wang, Xiaoheng Lu, Pingping Qiao, Yifei Jin, Jun Yu, Qi Chen, Hongkui Wang
Summary: Matrix metalloproteinase 9 (MMP9) is an important gene up-regulated during peripheral nerve regeneration, and it plays a significant role in Schwann cell migration and phenotype modulation. The direct application of MMP9 recombinant protein enhances the regeneration process in injured rats by promoting Schwann cell migration, blood vessel formation, axon elongation, and myelin wrapping. MMP9 regulates both the extracellular and intracellular metabolism of Schwann cells.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Engineering, Biomedical
Xianhao Dong, Siyang Liu, Yueyue Yang, Shan Gao, Wenlei Li, Jiasong Cao, Ye Wan, Ziqi Huang, Guanwei Fan, Quan Chen, Hongjun Wang, Meifeng Zhu, Deling Kong
Summary: Research on nerve conduits composed of oriented microfiber-bundle cores and randomly organized nanofiber sheaths has shed light on the regulatory role of microfiber orientation in promoting peripheral nerve regeneration, elucidating a cascade of biological responses and ultimately enhancing nerve regeneration outcomes.
Article
Neurosciences
Emily L. Errante, Anthony Diaz, Taylor Smartz, Aisha Khan, Risset Silvera, Adriana E. Brooks, Yee-Shuan Lee, S. Shelby Burks, Allan D. Levi
Summary: Peripheral nerve injury (PNI) is common in trauma patients, and severe PNI can be challenging to treat. The use of cell therapies, particularly Schwann cells, has shown effectiveness in PNI treatment. Our laboratory has demonstrated the effectiveness of Schwann cells in the treatment of severe PNI when used with axon guidance channels, but optimal cellular placement techniques are crucial.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Liam A. McMorrow, Adrian Kosalko, Daniel Robinson, Alberto Saiani, Adam J. Reid
Summary: Patients with major peripheral nerve injury have poor recovery outcomes due to slow axonal regeneration and deterioration in the ability of the distal stump to support axonal growth. Schwann cells play a crucial role in nerve regeneration, but chronic denervation leads to instability in their repair phenotype and hinders regeneration support. Recent research on the cellular machinery, particularly the role of c-Jun, has opened opportunities for therapeutic intervention to support prolonged neural regeneration.
Article
Immunology
Jiawei Xu, Jinkun Wen, Lanya Fu, Liqiang Liao, Ying Zou, Jiaqi Zhang, Junyao Deng, Haowen Zhang, Jingmin Liu, Xianghai Wang, Daming Zuo, Jiasong Guo
Summary: The depletion of RhoA in macrophages has a negative impact on Wallerian degeneration and nerve regeneration, mainly due to impaired migration and phagocytosis of macrophages resulting from disrupted RhoA/ROCK/MLCK pathway. Since previous research has shown that RhoA inhibition in neurons promotes axonal regeneration, the study highlights the importance of considering cellular specificity of RhoA-targeted drugs in future applications for treating peripheral nerve injuries.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Orthopedics
Guidong Shi, Dingyu Hao, Lei Zhang, Jia Qin, Guangyuan Tian, Boyuan Ma, Xianhu Zhou
Summary: Through analysis of normal and activated Schwann cells, this study identified key genes and proteins involved in endocytosis and exosomes which may control the molecular mechanism of peripheral nerve repair. The study suggests that targeting endocytosis-associated pathways in Schwann cells could be a novel therapeutic approach for nerve tissue engineering and regeneration.
JOURNAL OF ORTHOPAEDIC TRANSLATION
(2021)
Article
Cell Biology
Dandan Tan, Haowen Zhang, Junyao Deng, Jingmin Liu, Jinkun Wen, Lixia Li, Xianghai Wang, Mengjie Pan, Xiaofang Hu, Jiasong Guo
Article
Neurosciences
Muhua Lai, Mengjie Pan, Longjiao Ge, Jingmin Liu, Junyao Deng, Xianghai Wang, Lixia Li, Jinkun Wen, Dandan Tan, Haowen Zhang, Xiaofang Hu, Lanya Fu, Yizhou Xu, Zhenlin Li, Xiaozhong Qiu, Gong Chen, Jiasong Guo
EXPERIMENTAL NEUROLOGY
(2020)
Article
Cell & Tissue Engineering
Qingzha Deng, Sunxing Huang, Jinkun Wen, Yiren Jiao, Xiaohu Su, Guang Shi, Junjiu Huang
STEM CELL RESEARCH & THERAPY
(2020)
Article
Engineering, Biomedical
Xiaofang Hu, Xianghai Wang, Yizhou Xu, Lixia Li, Jingmin Liu, Yutong He, Ying Zou, Lei Yu, Xiaozhong Qiu, Jiasong Guo
ADVANCED HEALTHCARE MATERIALS
(2020)
Article
Engineering, Biomedical
Yazhong Bu, Xianghai Wang, Lixia Li, Xiaofang Hu, Dandan Tan, Zhenlin Li, Muhua Lai, Xiaozhong Qiu, Feifei Sun, Hufei Wang, Fei Yang, Decheng Wu, Jiasong Guo
ADVANCED HEALTHCARE MATERIALS
(2020)
Article
Pharmacology & Pharmacy
Yan Qin, Bin Zheng, Gao-shan Yang, Jing Zhou, Hao-jie Yang, Zi-yuan Nie, Tian-rui Wang, Xin-hua Zhang, Hong-ye Zhao, Jian-hong Shi, Jin-kun Wen
EUROPEAN JOURNAL OF PHARMACOLOGY
(2020)
Article
Biochemical Research Methods
Jinkun Wen, Jinni Wu, Tianqi Cao, Shengyao Zhi, Yuxi Chen, Lars Aagaard, Peilin Zhen, Yanming Huang, Jianxin Zhong, Junjiu Huang
Summary: The study shows that in a mouse model generated by lentiviral transduction, exogenous genes can be silenced by DNA methylation, with methylation density increasing during reproduction. However, the methyltransferase inhibitor 5-azacytidine can reactivate silenced genes in neonatal mice, providing a safe and efficient way to achieve stable transgene expression.
TRANSGENIC RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Jinkun Wen, Tianqi Cao, Jinni Wu, Yuxi Chen, Shengyao Zhi, Yanming Huang, Peilin Zhen, Guanglan Wu, Lars Aagaard, Jianxin Zhong, Puping Liang, Junjiu Huang
Summary: This study established a humanized mouse model to mimic TTR amyloidosis and compared the efficiency of reducing mutant protein expression using dual adeno-associated virus (AAV8)-mediated split SpCas9 and single AAV8-mediated Nme2Cas9 systems. The results showed that the single AAV-mediated Nme2Cas9 system was more effective in reducing mutant protein expression, providing proof of principle for gene therapy for TTR amyloidosis.
Article
Immunology
Jiawei Xu, Jinkun Wen, Lanya Fu, Liqiang Liao, Ying Zou, Jiaqi Zhang, Junyao Deng, Haowen Zhang, Jingmin Liu, Xianghai Wang, Daming Zuo, Jiasong Guo
Summary: The depletion of RhoA in macrophages has a negative impact on Wallerian degeneration and nerve regeneration, mainly due to impaired migration and phagocytosis of macrophages resulting from disrupted RhoA/ROCK/MLCK pathway. Since previous research has shown that RhoA inhibition in neurons promotes axonal regeneration, the study highlights the importance of considering cellular specificity of RhoA-targeted drugs in future applications for treating peripheral nerve injuries.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Cell Biology
Jingmin Liu, Lixia Li, Ying Zou, Lanya Fu, Xinrui Ma, Haowen Zhang, Yizhou Xu, Jiawei Xu, Jiaqi Zhang, Mi Li, Xiaofang Hu, Zhenlin Li, Xianghai Wang, Hao Sun, Hui Zheng, Lixin Zhu, Jiasong Guo
Summary: Wallerian degeneration, the degeneration of distal axons and myelin after nerve injury, is crucial for nerve regeneration. This study found that microtubule dynamics are involved in this process, with microtubule stabilization promoting degeneration and dedifferentiation, while microtubule destabilization inhibiting these processes.
NEURAL REGENERATION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ying Zou, Jiaqi Zhang, Jiawei Xu, Lanya Fu, Yizhou Xu, Xianghai Wang, Zhenlin Li, Lixin Zhu, Hao Sun, Hui Zheng, Jiasong Guo
Summary: SIRT6 plays a crucial role in macrophage function following peripheral nerve injury, with its inhibition impairing migration, phagocytosis, and M2 polarization of macrophages, thus suggesting it as a potential therapeutic target for peripheral nerve injury.
CELL AND BIOSCIENCE
(2021)
Article
Neurosciences
Changnan Xie, Yihan Wang, Jinfeng Wang, Yizhou Xu, Haining Liu, Jiasong Guo, Lixin Zhu
Summary: This study found that Perlecan is specifically expressed in the basement membranes (BMs) of the spinal cord and undergoes degradation/remodeling after spinal cord injury (SCI). Overexpression of Perlecan significantly enhances locomotor recovery and neural regeneration, reduces blood-spinal cord barrier (BSCB) permeability, and decreases the neuroinflammatory response. Perlecan interacts with integrin beta 1 and inhibits downstream signaling pathway to improve BSCB integrity.
MOLECULAR NEUROBIOLOGY
(2023)