title: Secretion of bacterial chondroitinase ABC from bone marrow stromal cells by glycosylation site mutation: a promising approach for axon regeneration.
abstract: Growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) contribute a lot to failure of axon regeneration. Chondroitinase ABC (ChABC) digests glycosaminoglycan chains attached in CSPGs and can thereby promote axonal regeneration beyond a lesion site. However, CSPGs expression are up-regulated for almost 7 weeks after spinal cord injury (SCI) in vivo, so single dose of exogenous ChABC is insufficient for long distance of axon sprout and functional recovery. It is considered an ideal strategy to transfect neurons and/or glia at the injury site with a vector containing the gene encoding chondroitinase, so they can secrete ChABC themselves. Mammalian cells in the current studies, however, can not secret ChABC efficiently. It is well established that glycosylation is a common obstacle for eukaryotic cells to secret bacterial protein. ChABC is a protein heavily glycosylated structurally, and it was reported that inhibiting the glycosylation of xylosyltransferase-1 with a DNA enzyme could reduce GAG chains in the lesion of spinal cord. So presence of glycosylation sites in the bacterial sequence is supposed the barrier that preventing ChABC secretion from mammalian cells. We intend to mutate the key N-glycosylation sites of the bacterial ChABC sequence and transduce it into BMSCs by lentivirus vector. The modified BMSCs are expected to promote axon regeneration through multiple mechanisms, providing sustained ChABC and neurotrophic factors, as well as filling in the cavities formed post-trauma. The transduced BMSCs with gene mutated in key glycosylation sites in the present hypothesis provide a promising strategy to promote axon regeneration.
authors: Department of Orthopaedics, Renmin Hospital, Wuhan University, Wuhan City 430060, China. martin1354@163.com
authors: Yonggang
authors: Y
authors: Ma
authors: Min
authors: M
authors: Liu
authors: Yaming
authors: Y
authors: Li
mesh_terms: D001369:Axons; D001419:Bacteria / Q000201:enzymology*; D001854:Bone Marrow Cells / Q000378:metabolism*; D019765:Chondroitin ABC Lyase / Q000378:metabolism*; D006031:Glycosylation; D008962:Models, Theoretical; D009154:Mutation; D012038:Regeneration; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D019765:Chondroitin ABC Lyase