Ablation of Lrp4 in Schwann Cells Promotes Peripheral Nerve Regeneration in Mice. 2021

Tian-Kun Hui, and Xin-Sheng Lai, and Xia Dong, and Hongyang Jing, and Ziyang Liu, and Erkang Fei, and Wen-Bing Chen, and Shunqi Wang, and Dongyan Ren, and Suqi Zou, and Hai-Tao Wu, and Bing-Xing Pan
School of Life Sciences, Nanchang University, Nanchang 330031, China.

Low-density lipoprotein receptor-related protein 4 (Lrp4) is a critical protein involved in the Agrin-Lrp4-MuSK signaling pathway that drives the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ). Many studies have shown that Lrp4 also functions in kidney development, bone formation, nervous system development, etc. However, whether Lrp4 participates in nerve regeneration in mammals remains unknown. Herein, we show that Lrp4 is expressed in SCs and that conditional knockout (cKO) of Lrp4 in SCs promotes peripheral nerve regeneration. In Lrp4 cKO mice, the demyelination of SCs was accelerated, and the proliferation of SCs was increased in the injured nerve. Furthermore, we identified that two myelination-related genes, Krox-20 and Mpz, were downregulated more dramatically in the cKO group than in the control group. Our results elucidate a novel role of Lrp4 in peripheral nerve regeneration and thereby provide a potential therapeutic target for peripheral nerve recovery.

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