Possible Impedance of Luminal Reepithelialization by Tracheal Cartilage Metalloproteinases

Sigurdson, Lynn; Sen, Tuhina; Hall, Leon; Rubenfeld, Ari B.; Hard, R; Gardella, Joseph A.; Bright, Frank V.; Hicks, Wesley L.

doi:10.1001/archotol.129.2.197

Cited by 11 publications

(8 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MMP2 and 9 are produced by cartilage from the trachea and bronchus, and cartilage conditioned medium decreases respiratory epithelial cell proliferation in vitro (Sigurdson et al, 2003). Addition of a broad, spectrum MMP inhibitor, GM6001, to this culture medium rescues epithelial cell proliferation suggesting that at least some of the MMPs produced by the cartilage repress respiratory cell proliferation (Sigurdson et al, 2003).…”

Section: Metalloproteinases In Epithelial Repairmentioning

confidence: 99%

Metalloproteinases and their inhibitors: Regulators of wound healing

Gill

Parks

2008

The International Journal of Biochemistry & Cell Biology

642

524

View full text Add to dashboard Cite

Wound healing is a dynamic process that involves a coordinated response of many cell types representing distinct tissue compartments and is fundamentally similar among tissue types. Among the many gene products that are essential for restoration normal tissue architecture, several members of the matrix metalloproteinase (MMP) function as positive and, at times, negative regulators of repair processes. MMPs were initially thought to only function in the resolution phase of wound healing, particularly during scar resorption; however, recent evidence suggests that they also influence other wound-healing responses, such as inflammation and re-epithelialization. In this review, we discuss what is currently known about the function of MMPs in wound healing and will provide suggestions for future research directions.

show abstract

Section: Metalloproteinases In Epithelial Repairmentioning

confidence: 99%

Metalloproteinases and their inhibitors: Regulators of wound healing

Gill

Parks

2008

The International Journal of Biochemistry & Cell Biology

642

524

View full text Add to dashboard Cite

show abstract

“…MMP-9 is the most prominently studied MMP in the lung and has been associated with a variety of lung diseases (4). The imbalance between MMP-9 and TIMP-1 is considered to contribute to the progression of airway remodeling in part due to changes in epithelial wound response (4,6,12,29,39,47,48).…”

mentioning

confidence: 99%

Arsenic upregulates MMP-9 and inhibits wound repair in human airway epithelial cells

Olsen

Liguori

Zong

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

As part of the innate immune defense, the polarized conducting lung epithelium acts as a barrier to keep particulates carried in respiration from underlying tissue. Arsenic is a metalloid toxicant that can affect the lung via inhalation or ingestion. We have recently shown that chronic exposure of mice or humans to arsenic (10-50 ppb) in drinking water alters bronchiolar lavage or sputum proteins consistent with reduced epithelial cell migration and wound repair in the airway. In this report, we used an in vitro model to examine effects of acute exposure of arsenic (15-290 ppb) on conducting airway lung epithelium. We found that arsenic at concentrations as low as 30 ppb inhibits reformation of the epithelial monolayer following scrape wounds of monolayer cultures. In an effort to understand functional contributions to epithelial wound repair altered by arsenic, we showed that acute arsenic exposure increases activity and expression of matrix metalloproteinase (MMP)-9, an important protease in lung function. Furthermore, inhibition of MMP-9 in arsenic-treated cells improved wound repair. We propose that arsenic in the airway can alter the airway epithelial barrier by restricting proper wound repair in part through the upregulation of MMP-9 by lung epithelial cells.

show abstract

“…The involvement of MMPs, and particularly MMP-9, in airway wound repair and cell migration has already been reported in other studies (11,39). In contrast, it has been shown that MMP-2 and MMP-9 in conditioned medium from tracheal cartilage inhibit the adherence and proliferation of tracheal epithelial cells, an effect prevented by GM6001 (53).…”

Section: Discussionmentioning

confidence: 53%

Regulation of normal and cystic fibrosis airway epithelial repair processes by TNF-α after injury

Maillé

Trinh

Privé

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Chronic infection and inflammation have been associated with progressive airway epithelial damage in patients with cystic fibrosis (CF). However, the effect of inflammatory products on the repair capacity of respiratory epithelia is unclear. Our objective was to study the regulation of repair mechanisms by tumor necrosis factor-α (TNF-α), a major component of inflammation in CF, in a model of mechanical wounding, in two bronchial cell lines, non-CF NuLi and CF CuFi. We observed that TNF-α enhanced the NuLi and CuFi repair rates. Chronic exposure (24-48 h) to TNF-α augmented this stimulation as well as the migration rate during repair. The cellular mechanisms involved in this stimulation were then evaluated. First, we discerned that TNF-α induced metalloproteinase-9 release, epidermal growth factor (EGF) shedding, and subsequent EGF receptor transactivation. Second, TNF-α-induced stimulation of the NuLi and CuFi wound-closure rates was prevented by GM6001 (metalloproteinase inhibitor), EGF antibody (to titrate secreted EGF), and EGF receptor tyrosine kinase inhibitors. Furthermore, we recently reported a relationship between the EGF response and K(+) channel function, both controlling bronchial repair. We now show that TNF-α enhances KvLQT1 and K(ATP) currents, while their inhibition abolishes TNF-α-induced repair stimulation. These results indicate that the effect of TNF-α is mediated, at least in part, through EGF receptor transactivation and K(+) channel stimulation. In contrast, cell proliferation during repair was slowed by TNF-α, suggesting that TNF-α could exert contrasting actions on repair mechanisms of CF airway epithelia. Finally, the stimulatory effect of TNF-α on airway wound repair was confirmed on primary airway epithelial cells, from non-CF and CF patients.

show abstract

Possible Impedance of Luminal Reepithelialization by Tracheal Cartilage Metalloproteinases

Abstract: Cartilage production and activity of MMP after injury to the large conducting airway may be a factor in the failure of luminal reepithelialization, resulting in aberrant repair.

Cited by 11 publications

References 22 publications

Metalloproteinases and their inhibitors: Regulators of wound healing

Metalloproteinases and their inhibitors: Regulators of wound healing

Arsenic upregulates MMP-9 and inhibits wound repair in human airway epithelial cells

Regulation of normal and cystic fibrosis airway epithelial repair processes by TNF-α after injury

Contact Info

Product

Resources

About