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However, the role of RhoA in Schwann cells during nerve injury and repair is still unknown. Herein, we developed two lines of Schwann cells conditional RhoA knockout (cKO) mice by breeding RhoA<jats:sup>flox<\/jats:sup><jats:sup>\/<\/jats:sup><jats:sup>flox<\/jats:sup> mice with Plp<jats:sup>Cre<\/jats:sup><jats:sup>\u2010ERT2<\/jats:sup> or Dhh<jats:sup>Cre<\/jats:sup> mice. Our results indicate that RhoA cKO in Schwann cells accelerates axonal regrowth and remyelination after sciatic nerve injury, which enhances the recovery of nerve conduction and hindlimb gait, and alleviates the amyotrophy in gastrocnemius muscle. Mechanistic studies in both in vivo and in vitro models revealed that RhoA cKO could facilitate Schwann cell dedifferentiation via JNK pathway. Schwann cell dedifferentiation subsequently promotes Wallerian degeneration by enhancing phagocytosis and myelinophagy, as well as stimulating the production of neurotrophins (NT\u20103, NGF, BDNF, and GDNF). These findings shed light on the role of RhoA in Schwann cells during nerve injury and repair, indicating that cell type\u2010specific RhoA targeting could serve as a promising molecular therapeutic strategy for peripheral nerve injury.<\/jats:p>","DOI":"10.1002\/glia.24365","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T09:07:15Z","timestamp":1679908035000},"page":"1715-1728","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Schwann cell\u2010specific <scp>RhoA<\/scp> knockout accelerates peripheral nerve regeneration via promoting Schwann cell dedifferentiation"],"prefix":"10.1002","volume":"71","author":[{"given":"Jingmin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences Southern Medical University  Guangzhou 510515 China"},{"name":"Department of Spine Orthopedics, Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinkun","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"He","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences Southern Medical University  Guangzhou 510515 China"},{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong\u2010Hong Kong\u2010Macao Greater Bay Area Center for Brain Science and Brain\u2010Inspired Intelligence Guangdong Province Key Laboratory of Psychiatric Disorders  Guangzhou 510515 China"},{"name":"National Experimental Education Demonstration Center for Basic Medical Sciences, National Virtual &amp; 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