title: Up-Regulation of the Biosynthesis and Release of Substance P through Wnt/β-Catenin Signaling Pathway in Rat Dorsal Root Ganglion Cells.
abstract: To examine regulatory effects of β-catenin on the biosynthesis and release of substance P, a rat chronic constriction injury (CCI) model and a rat dorsal root ganglion (DRG) cell culture model were used in the present study. The CCI treatment significantly induced the overall expression of β-catenin (158 ± 6% of sham) in the ipsilateral L5 DRGs in comparison with the sham group (109 ± 4% of sham). The CCI-induced aberrant expression of β-catenin was significantly attenuated by oral administration of diclofenac (119 ± 6% of the sham value; 10 mg/kg). Importantly, aberrant nuclear accumulation of β-catenin in cultured DRG cells resulted in up-regulation of the PPT-A mRNA expression and the substance P release. The up-regulation of both the PPT-A mRNA expression and the substance P release by either a GSK-3β inhibitor TWS119 (10 μM) or a Wnt signaling agonist Wnt-3a (100 ng/ml) were significantly abolished by an inhibitor of cyclooxygenase-2 (COX-2; NS-398, 1 μM). Collectively, these data suggest that nociceptive input-activated β-catenin signaling plays an important role in regulating the biosynthesis and release of substance P, which may contribute to the inflammation responses related to chronic pain.
authors.affiliation: Department of Pharmacology, College of Pharmacy, South-Central University for Nationalities, No. 182 Minyuan Road, Hongshan-qu, Wuhan 430074, China.
authors.forename: Yu-Sang
authors.initials: YS
authors.lastname: Li
authors.affiliation: Medical School, Ningbo University, No. 818 Fenghua Road, Jiangbei District, Ningbo 315211, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Pharmacology, College of Pharmacy, South-Central University for Nationalities, No. 182 Minyuan Road, Hongshan-qu, Wuhan 430074, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Department of Pharmacology, College of Pharmacy, South-Central University for Nationalities, No. 182 Minyuan Road, Hongshan-qu, Wuhan 430074, China.
authors.forename: Chang-Long
authors.initials: CL
authors.lastname: Leng
authors.affiliation: Department of Pharmacology, College of Pharmacy, South-Central University for Nationalities, No. 182 Minyuan Road, Hongshan-qu, Wuhan 430074, China.
authors.forename: Mei-Mei
authors.initials: MM
authors.lastname: Jia
authors.affiliation: Department of Pharmacology, College of Pharmacy, South-Central University for Nationalities, No. 182 Minyuan Road, Hongshan-qu, Wuhan 430074, China.
authors.forename: Wei Kevin
authors.initials: WK
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, College of Pharmacy, South-Central University for Nationalities, No. 182 Minyuan Road, Hongshan-qu, Wuhan 430074, China.
authors.forename: He-Bin
authors.initials: HB
authors.lastname: Tang
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology* / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D059348:Peripheral Nerve Injuries / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D013373:Substance P / Q000378:metabolism*; D014158:Transcription, Genetic; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D051176:beta Catenin; D013373:Substance P; D051546:Cyclooxygenase 2