| First Author | Li X | Year | 2016 |
| Journal | Oxid Med Cell Longev | Volume | 2016 |
| Pages | 7894247 | PubMed ID | 27648120 |
| Mgi Jnum | J:315458 | Mgi Id | MGI:6830479 |
| Doi | 10.1155/2016/7894247 | Citation | Li X, et al. (2016) Cathepsin B Regulates Collagen Expression by Fibroblasts via Prolonging TLR2/NF-kappaB Activation. Oxid Med Cell Longev 2016:7894247 |
| abstractText | 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 mug/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 IkappaBalpha. Furthermore, the P.g. LPS-increased 8-OHdG and decreased IkappaBalpha 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-kappaB activation and oxidative stress. CatB-specific inhibitors may therefore improve chronic inflammation-delayed tissue repair. |
