The effects of the M2a macrophage-induced axonal regeneration of neurons by arginase 1
Authors: Changmei Weng
Guanhua Li
Lu Zhang
Jianyi Kang
Zhaoxia Duan
Jianmin Wang
Bingcang Li
Dongdong Zhang
Jieyuan Zhang
Kuijun Chen
Yue Li
Journal: Bioscience reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Arg1; Cdc42/N-WASP; M2a; Spinal cord injury; macrophage.
Affiliations: Daping Hospital, Army Medical University, State Key Laboratory of Trauma, Burn and Combined Injury, 400042 Chongqing, People's Republic of China., Xinan Hospital, Army Medical University, 400038 Chongqing, People's Republic of China., Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing 400014, China.

Abstract:  Background: Spinal cord injury (SCI) is a challenge worldwide, but there are no effective treatments or therapeutic methods in the clinic. Recent studies have shown that type I arginase (Arginase1, Arg1) is closely associated with the treatment of SCI. The classical treatment for SCI involves filling the local area of SCI with activated M2a macrophages to allow the repair and regeneration of some synapses, but the specific mechanism of action of Arg1 is not clear. Method: In the present study, we first induced the polarization of RAW264.7 macrophages to M2a-type cells using IL-4 and constructed an Arg1 knockout cell line through the use of shRNA; we used these cells to treat a rat model of SCI. Finally, the present study explored the mechanism and pathway by which Arginase 1 regulates spinal repair by immunoblotting and immunohistochemistry. Result: Suspended M2a (Arg1-/+) macrophages were transplanted into the injury site in a rat model of contusion SCI. Compared with the model group and the shArg1 group, the shScramble (shSc) group exhibited higher Basso, Beattie, Bresnahan motor function scores, more compact structures and more Nissl bodies. Immunohistochemical results showed that the shSc group expressed higher levels of NeuN (a neuronal marker) and tau (an axonal marker), as well as the up-regulation of Cdc42, N-WASP, Arp2/3 and tau, as determined by Western blot. Conclusion: The study found that the polarization of M2a macrophages promoted the expression of Arginase 1, which restored axonal regeneration, promoted axonal regeneration, and promoted the structural and functional recovery of the contused spinal cord. 

Retracted: No

PubPeer comments:
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