title: Cathepsin B Regulates Collagen Expression by Fibroblasts via Prolonging TLR2/NF-κB Activation.
abstract: Fibroblasts are essential for tissue repair due to producing collagens, and lysosomal proteinase cathepsin B (CatB) is involved in promoting chronic inflammation. We herein report that CatB regulates the expression of collagens III and IV by fibroblasts in response to a TLR2 agonist, lipopolysaccharide from Porphyromonas gingivalis (P.g. LPS). In cultured human BJ fibroblasts, mRNA expression of CatB was significantly increased, while that of collagens III and IV was significantly decreased at 24 h after challenge with P.g. LPS (1 μg/mL). The P.g. LPS-decreased collagen expression was completely inhibited by CA-074Me, the specific inhibitor of CatB. Surprisingly, expression of collagens III and IV was significantly increased in the primary fibroblasts from CatB-deficient mice after challenge with P.g. LPS. The increase of CatB was accompanied with an increase of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and a decrease of IκBα. Furthermore, the P.g. LPS-increased 8-OHdG and decreased IκBα were restored by CA-074Me. Moreover, 87% of CatB and 86% of 8-OHdG were colocalized with gingival fibroblasts of chronic periodontitis patients. The findings indicate the critical role of CatB in regulating the expression of collagens III and IV by fibroblasts via prolonging TLR2/NF-κB activation and oxidative stress. CatB-specific inhibitors may therefore improve chronic inflammation-delayed tissue repair.
authors.affiliation: Department of Implantology, School of Stomatology, Jilin University, Changchun 130021, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan; OBT Research Center, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Zhou
authors.identifier: 0000-0002-4910-9037
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Junjun
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yicong
authors.identifier: 0000-0002-7520-2411
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Jie
authors.initials: J
authors.lastname: Meng
authors.affiliation: Department of Implantology, School of Stomatology, Jilin University, Changchun 130021, China.
authors.forename: Weixian
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Department of Implantology, School of Stomatology, Jilin University, Changchun 130021, China.
authors.forename: Yanmin
authors.identifier: 0000-0002-4173-6765
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000818:Animals; D002401:Cathepsin B / Q000378:metabolism*; D055113:Chronic Periodontitis / Q000150:complications / Q000382:microbiology / Q000473:pathology; D024061:Collagen Type III / Q000378:metabolism*; D024141:Collagen Type IV / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008875:Middle Aged; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D016966:Porphyromonas gingivalis / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: D024061:Collagen Type III; D024141:Collagen Type IV; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D002401:Cathepsin B