机构：[1]Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.[2]Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.[3]Department of Disease prevention and control, Xijing 986 Hospital, The Fourth Military Medical University, Shanxi 710000, China.[4]Department of Anesthesiology (High-Tech Branch), The First Affiliated Hospital of Anhui Medical University, Hefei 230080, China.[5]Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, China.[6]The Center for Scientific Research of the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.[7]Department of Otolaryngology-Head and Neck Surgery, Key Laboratory of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.临床科室耳鼻咽喉-头颈外科首都医科大学附属北京同仁医院首都医科大学附属同仁医院
Wallerian degeneration (WD) involves the recruitment of macrophages for debris clearance and nerve regeneration, and the cause of the foamy macrophages that are frequently observed in peripheral transection injuries is unknown. Recent studies indicated that these foamy cells are generated by gasdermin D (GSDMD) via membrane perforation. However, whether these foamy cells are pyroptotic macrophages and whether their cell death elicits immunogenicity in peripheral nerve regeneration (PNR) remain unknown. Therefore, we used GSDMD-deficient mice and mice with deficiencies in other canonical inflammasomes to establish a C57BL/6 J mouse model of sciatic nerve transection and microanastomosis (SNTM) and evaluate the role of GSDMD-executed pyroptosis in PNR. In our study, the GSDMD-/- mice with SNTM showed a significantly diminished number of foamy cells, better axon regeneration, and a favorable functional recovery, whereas irregular axons or gaps in the fibers were found in the wild-type (WT) mice with SNTM. Furthermore, GSDMD activation in the SNTM model was dependent on the NLRP3 inflammasome and caspase-1 activation, and GSDMD-executed pyroptosis resulted in a proinflammatory environment that polarized monocytes/macrophages toward the M1 (detrimental) but not the M2 (beneficial) phenotype. In contrast, depletion of GSDMD reversed the proinflammatory microenvironment and facilitated M2 polarization. Our results suggested that inhibition of GSDMD may be a potential treatment option to promote PNR.
基金：
National Natural Science Foundation of China (Grant 82071032), National Natural
Science Foundation of China (Grant 82071775), The China Postdoctoral Science
Foundation (2019M652215), the initial research fund of the First Affiliated Hospital of
Anhui Medical University, the Fundamental Research Funds for the Central
Universities (WK2070000149), the new Medicine Fund of the University of Science
and Technology of China (WK2070000170), and the Natural Science Research Project
of Anhui Higher Education Institution (KJ2018ZD021), and the Scientific Research
Project of the Anhui Health Commission (AHWJ2021b160) supported this work.
第一作者机构：[1]Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Tao Ye,Wang Fang,Xu Zhaohui,et al.Gasdermin D in peripheral nerves: the pyroptotic microenvironment inhibits nerve regeneration.[J].CELL DEATH DISCOVERY.2021,7(1):doi:10.1038/s41420-021-00529-6.
APA：
Tao Ye,Wang Fang,Xu Zhaohui,Lu Xianfu,Yang Yanqing...&Liu Yehai.(2021).Gasdermin D in peripheral nerves: the pyroptotic microenvironment inhibits nerve regeneration..CELL DEATH DISCOVERY,7,(1)
MLA：
Tao Ye,et al."Gasdermin D in peripheral nerves: the pyroptotic microenvironment inhibits nerve regeneration.".CELL DEATH DISCOVERY 7..1(2021)
