title: Transmembrane proteoglycans syndecan-2, 4, receptor candidates for the impact of HGF and FGF2 on semaphorin 3A expression in early-differentiated myoblasts.
abstract: Regenerative mechanisms that regulate intramuscular motor innervation are thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies proposed an unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF2) triggered its expression exclusively at the early differentiation phase. In order to advance this concept, the present study described that transmembrane heparan/chondroitin sulfate proteoglycans syndecan-2, 4 may be the plausible receptor candidates for HGF and FGF2 to signal Sema3A expression. Results showed that mRNA expression of syndecan-2, 4 was abundant (two magnitudes higher than syndecan-1, 3) in early-differentiated myoblasts and their in vitro knockdown diminished the HGF/FGF2-induced expression of Sema3A down to a baseline level. Pretreatment with heparitinase and chondroitinase ABC decreased the HGF and FGF2 responses, respectively, in non-knockdown cultures, supporting a possible model that HGF and FGF2 may bind to heparan and chondroitin sulfate chains of syndecan-2, 4 to signal Sema3A expression. The findings, therefore, extend our understanding that HGF/FGF2-syndecan-2, 4 association may stimulate a burst of Sema3A secretion by myoblasts recruited to the site of muscle injury; this would ensure a coordinated delay in the attachment of motoneuron terminals onto fibers early in muscle regeneration, and thus synchronize the recovery of muscle fiber integrity and the early resolution of inflammation after injury with reinnervation toward functional recovery.
authors.affiliation: Department of Animal and Marine Bioresource Sciences Kyushu University, Fukuoka, Japan.
authors.forename: Mai-Khoi Q
authors.initials: MK
authors.lastname: Do
authors.affiliation: Department of Animal and Marine Bioresource Sciences Kyushu University, Fukuoka, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Shimizu
authors.affiliation: Department of Animal and Marine Bioresource Sciences Kyushu University, Fukuoka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Animal and Marine Bioresource Sciences Kyushu University, Fukuoka, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ohtsubo
authors.affiliation: Department of Animal and Marine Bioresource Sciences Kyushu University, Fukuoka, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Mizunoya
authors.affiliation: Graduate School of Agriculture, Kyushu University, Fukuoka, Japan.
authors.forename: Mako
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Animal and Marine Bioresource Sciences Kyushu University, Fukuoka, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Sawano
authors.affiliation: Department of Animal and Marine Bioresource Sciences Kyushu University, Fukuoka, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Furuse
authors.affiliation: Department of Animal and Marine Bioresource Sciences Kyushu University, Fukuoka, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Ikeuchi
authors.affiliation: Department of Biological Sciences, Faculty of Science, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Judy E
authors.initials: JE
authors.lastname: Anderson
authors.affiliation: Department of Animal and Marine Bioresource Sciences Kyushu University, Fukuoka, Japan rtatsumi@agr.kyushu-u.ac.jp.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Tatsumi
keywords: Basic fibroblast growth factor; hepatocyte growth factor; proteoglycans; semaphorin 3A; syndecans