Cathepsin B Regulates Collagen Expression by Fibroblasts via Prolonging TLR2/NF-κB Activation

Xue Li, Zhou Wu, Junjun Ni, Yicong Liu, Jie Meng, Weixian Yu, Hiroshi Nakanishi, Yanmin Zhou

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Article number7894247
JournalOxidative medicine and cellular longevity
Volume2016
DOIs
Publication statusPublished - Jan 1 2016

Fingerprint

Cathepsin B
Fibroblasts
Collagen
Chemical activation
yeast proteinase B
Repair
Tissue
Inflammation
Chronic Periodontitis
Porphyromonas gingivalis
Oxidative stress
Lipopolysaccharides
Oxidative Stress
Peptide Hydrolases
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Ageing
  • Cell Biology

Cite this

Cathepsin B Regulates Collagen Expression by Fibroblasts via Prolonging TLR2/NF-κB Activation. / Li, Xue; Wu, Zhou; Ni, Junjun; Liu, Yicong; Meng, Jie; Yu, Weixian; Nakanishi, Hiroshi; Zhou, Yanmin.

In: Oxidative medicine and cellular longevity, Vol. 2016, 7894247, 01.01.2016.

Research output: Contribution to journalArticle

Li, Xue ; Wu, Zhou ; Ni, Junjun ; Liu, Yicong ; Meng, Jie ; Yu, Weixian ; Nakanishi, Hiroshi ; Zhou, Yanmin. / Cathepsin B Regulates Collagen Expression by Fibroblasts via Prolonging TLR2/NF-κB Activation. In: Oxidative medicine and cellular longevity. 2016 ; Vol. 2016.
@article{8aec100004e344d9a88d29f1f22643db,
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.",
author = "Xue Li and Zhou Wu and Junjun Ni and Yicong Liu and Jie Meng and Weixian Yu and Hiroshi Nakanishi and Yanmin Zhou",
year = "2016",
month = "1",
day = "1",
doi = "10.1155/2016/7894247",
language = "English",
volume = "2016",
journal = "Oxidative Medicine and Cellular Longevity",
issn = "1942-0900",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - Cathepsin B Regulates Collagen Expression by Fibroblasts via Prolonging TLR2/NF-κB Activation

AU - Li, Xue

AU - Wu, Zhou

AU - Ni, Junjun

AU - Liu, Yicong

AU - Meng, Jie

AU - Yu, Weixian

AU - Nakanishi, Hiroshi

AU - Zhou, Yanmin

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84987924159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84987924159&partnerID=8YFLogxK

U2 - 10.1155/2016/7894247

DO - 10.1155/2016/7894247

M3 - Article

C2 - 27648120

AN - SCOPUS:84987924159

VL - 2016

JO - Oxidative Medicine and Cellular Longevity

JF - Oxidative Medicine and Cellular Longevity

SN - 1942-0900

M1 - 7894247

ER -