Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 180 - 192 |
| Number of pages | 13 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 50 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2014 |
Cite this
}
Mechanistic insights into the contribution of epithelial damage to airway remodeling. Novel therapeutic targets for asthma. / Royce, Simon G; Li, Xuelei; Tortorella, Stephanie; Goodings, Liana Maree; Chow, Bryna SM; Giraud, Andrew S; Tang, Mimi L K; Samuel, Chrishan S.
In: American Journal of Respiratory Cell and Molecular Biology, Vol. 50, No. 1, 2014, p. 180 - 192.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Mechanistic insights into the contribution of epithelial damage to airway remodeling. Novel therapeutic targets for asthma
AU - Royce, Simon G
AU - Li, Xuelei
AU - Tortorella, Stephanie
AU - Goodings, Liana Maree
AU - Chow, Bryna SM
AU - Giraud, Andrew S
AU - Tang, Mimi L K
AU - Samuel, Chrishan S
PY - 2014
Y1 - 2014
N2 - It has been suggested that an inherent airway epithelial repair defect is the root cause of airway remodeling in asthma. However, the relationship between airway epithelial injury and repair, airway remodeling, and airway hyperresponsiveness (AHR) has not been directly examined. We investigated the contribution of epithelial damage and repair to the development of airway remodeling and AHR using a validated naphthalene (NA)-induced murine model of airway injury. In addition, we examined the endogenous versus exogenous role of the epithelial repair peptide trefoil factor 2 (TFF2) in disease pathogenesis. A single dose of NA (200 mg/kg in 10 ml/kg bodyweight corn oil [CO] vehicle, intraperitoneally)was administered to mice. Control mice were treated with CO (10 ml/kg body weight, intraperitoneally).At 12, 24, 48, and 72hours afterNAorCOinjection, AHR and various measures of airway remodeling were examined by invasive plethysmography and morphometric analyses, respectively. TFF2-deficient mice and intranasal treatment were used to examine the role of the epithelial repair peptide. NA treatment induced denudation and apoptosis of airway epithelial cells, goblet cell metaplasia, elevated AHR, and increased levels of endogenous TFF2. Airway epithelial changes peaked at 12 hours after NA treatment whereas airway remodeling changes were observed from 48 hours. TFF2 was protective against epithelial damage and induced remodeling and was found tomediate organ protection via a platelet-derived growth factor-associated mechanism. Our findings directly demonstrate the contribution of epithelial damage to airway remodeling and AHR and suggest that preventing airway epithelial damage and promoting epithelial repairmay have therapeutic implications for asthma treatment. Copyright ? 2014 by the American Thoracic Society.
AB - It has been suggested that an inherent airway epithelial repair defect is the root cause of airway remodeling in asthma. However, the relationship between airway epithelial injury and repair, airway remodeling, and airway hyperresponsiveness (AHR) has not been directly examined. We investigated the contribution of epithelial damage and repair to the development of airway remodeling and AHR using a validated naphthalene (NA)-induced murine model of airway injury. In addition, we examined the endogenous versus exogenous role of the epithelial repair peptide trefoil factor 2 (TFF2) in disease pathogenesis. A single dose of NA (200 mg/kg in 10 ml/kg bodyweight corn oil [CO] vehicle, intraperitoneally)was administered to mice. Control mice were treated with CO (10 ml/kg body weight, intraperitoneally).At 12, 24, 48, and 72hours afterNAorCOinjection, AHR and various measures of airway remodeling were examined by invasive plethysmography and morphometric analyses, respectively. TFF2-deficient mice and intranasal treatment were used to examine the role of the epithelial repair peptide. NA treatment induced denudation and apoptosis of airway epithelial cells, goblet cell metaplasia, elevated AHR, and increased levels of endogenous TFF2. Airway epithelial changes peaked at 12 hours after NA treatment whereas airway remodeling changes were observed from 48 hours. TFF2 was protective against epithelial damage and induced remodeling and was found tomediate organ protection via a platelet-derived growth factor-associated mechanism. Our findings directly demonstrate the contribution of epithelial damage to airway remodeling and AHR and suggest that preventing airway epithelial damage and promoting epithelial repairmay have therapeutic implications for asthma treatment. Copyright ? 2014 by the American Thoracic Society.
UR - http://www.atsjournals.org/doi/pdf/10.1165/rcmb.2013-0008OC
U2 - 10.1165/rcmb.2013-0008OC
DO - 10.1165/rcmb.2013-0008OC
M3 - Article
VL - 50
SP - 180
EP - 192
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 1
ER -