title: Matrix metalloproteinase-8 is involved in dermal nerve growth: implications for possible application to pruritus from in vitro models.
abstract: Cutaneous nerve density is related to abnormal itch perception in dermatoses, such as atopic dermatitis and xerosis. However, the mechanisms underlying the elongation of dermal nerve fibers within the interstitial collagen (CoL) matrix are poorly understood. In this study, a culture system of rat dorsal root ganglion neurons consisting of type I CoL and a Boyden chamber containing a nerve growth factor (NGF) concentration gradient was used. Nerve fibers penetrating into type I CoL gel were observed in the presence of the NGF concentration gradient. Levels of matrix metalloproteinase-8 (MMP-8) mRNA and protein were increased in the cultured neurons and the conditioned medium, respectively. The nerve fiber penetration was dose dependently inhibited by MMP-8 blockers. Moreover, MMP-8 immunoreactivity was partially localized at growth cones in NGF-responsive nerve fibers. Semaphorin 3A stimulation also showed the opposite effects on these NGF-dependent events. Intriguingly, MMP-8 expression was upregulated by type I and III CoLs, which are substrates for this enzyme. These results suggested that MMP-8 is involved in sensory nerve growth within the interstitial CoL matrix through modulation by the axonal guidance molecules and/or extracellular matrix components. These findings provide insight into the development of pruritus involving skin nerve density.
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Tominaga
authors.forename: Suhandy
authors.initials: S
authors.lastname: Tengara
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kamo
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Takamori
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D020784:Matrix Metalloproteinase 8 / Q000502:physiology*; D020932:Nerve Growth Factor / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D011537:Pruritus / Q000628:therapy*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D040121:Semaphorin-3A / Q000378:metabolism; D012867:Skin / Q000294:innervation*
chemical_list: D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D040121:Semaphorin-3A; D003094:Collagen; D020932:Nerve Growth Factor; D020784:Matrix Metalloproteinase 8