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The Rise and Fall of Hyaluronan in Respiratory Diseases.

Lauer ME, Dweik RA, Garantziotis S, Aronica MA - Int J Cell Biol (2015)

Bottom Line: The HA that accumulates in inflamed airways is of a high molecular weight (>1600 kDa) but can be broken down into smaller fragments (<150 kDa) by inflammatory and disease-related mechanisms that have profound effects on HA pathobiology.During inflammation in the airways, HA is often covalently modified with heavy chains from inter-alpha-inhibitor via the enzyme tumor-necrosis-factor-stimulated-gene-6 (TSG-6) and this modification promotes the interaction of leukocytes with HA matrices at sites of inflammation.The clearance of HA and its return to normal levels is essential for the proper resolution of inflammation.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Institute, Cleveland Clinic, Cleveland, OH 44195, USA ; Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA.

ABSTRACT
In normal airways, hyaluronan (HA) matrices are primarily located within the airway submucosa, pulmonary vasculature walls, and, to a lesser extent, the alveoli. Following pulmonary injury, elevated levels of HA matrices accumulate in these regions, and in respiratory secretions, correlating with the extent of injury. Animal models have provided important insight into the role of HA in the onset of pulmonary injury and repair, generally indicating that the induction of HA synthesis is an early event typically preceding fibrosis. The HA that accumulates in inflamed airways is of a high molecular weight (>1600 kDa) but can be broken down into smaller fragments (<150 kDa) by inflammatory and disease-related mechanisms that have profound effects on HA pathobiology. During inflammation in the airways, HA is often covalently modified with heavy chains from inter-alpha-inhibitor via the enzyme tumor-necrosis-factor-stimulated-gene-6 (TSG-6) and this modification promotes the interaction of leukocytes with HA matrices at sites of inflammation. The clearance of HA and its return to normal levels is essential for the proper resolution of inflammation. These data portray HA matrices as an important component of normal airway physiology and illustrate its integral roles during tissue injury and repair among a variety of respiratory diseases.

No MeSH data available.


Related in: MedlinePlus

Overview of hyaluronan in respiratory disease: the lung is continuously exposed to external stimuli which can then impact HA synthesis and turnover. Factors such as type of stimuli, genetics, and the lung environment itself determine if resolution or persistent inflammation and HA changes persist.
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fig1: Overview of hyaluronan in respiratory disease: the lung is continuously exposed to external stimuli which can then impact HA synthesis and turnover. Factors such as type of stimuli, genetics, and the lung environment itself determine if resolution or persistent inflammation and HA changes persist.

Mentions: Considerable progress has been made over the past few decades in our understanding of the role of hyaluronan (HA) in pulmonary health and disease. Once thought to be an inert molecule of the extracellular matrix, a picture has emerged of HA as an important regulator of inflammation, airway hyperresponsiveness (AHR), edema, and fibrosis in the lung. This image has been made clearer by a significant number of investigations into a wide variety of different pulmonary diseases, environmental effects, and animal models of lung injury, which are summarized in this review (Figure 1).


The Rise and Fall of Hyaluronan in Respiratory Diseases.

Lauer ME, Dweik RA, Garantziotis S, Aronica MA - Int J Cell Biol (2015)

Overview of hyaluronan in respiratory disease: the lung is continuously exposed to external stimuli which can then impact HA synthesis and turnover. Factors such as type of stimuli, genetics, and the lung environment itself determine if resolution or persistent inflammation and HA changes persist.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4581576&req=5

fig1: Overview of hyaluronan in respiratory disease: the lung is continuously exposed to external stimuli which can then impact HA synthesis and turnover. Factors such as type of stimuli, genetics, and the lung environment itself determine if resolution or persistent inflammation and HA changes persist.
Mentions: Considerable progress has been made over the past few decades in our understanding of the role of hyaluronan (HA) in pulmonary health and disease. Once thought to be an inert molecule of the extracellular matrix, a picture has emerged of HA as an important regulator of inflammation, airway hyperresponsiveness (AHR), edema, and fibrosis in the lung. This image has been made clearer by a significant number of investigations into a wide variety of different pulmonary diseases, environmental effects, and animal models of lung injury, which are summarized in this review (Figure 1).

Bottom Line: The HA that accumulates in inflamed airways is of a high molecular weight (>1600 kDa) but can be broken down into smaller fragments (<150 kDa) by inflammatory and disease-related mechanisms that have profound effects on HA pathobiology.During inflammation in the airways, HA is often covalently modified with heavy chains from inter-alpha-inhibitor via the enzyme tumor-necrosis-factor-stimulated-gene-6 (TSG-6) and this modification promotes the interaction of leukocytes with HA matrices at sites of inflammation.The clearance of HA and its return to normal levels is essential for the proper resolution of inflammation.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Institute, Cleveland Clinic, Cleveland, OH 44195, USA ; Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA.

ABSTRACT
In normal airways, hyaluronan (HA) matrices are primarily located within the airway submucosa, pulmonary vasculature walls, and, to a lesser extent, the alveoli. Following pulmonary injury, elevated levels of HA matrices accumulate in these regions, and in respiratory secretions, correlating with the extent of injury. Animal models have provided important insight into the role of HA in the onset of pulmonary injury and repair, generally indicating that the induction of HA synthesis is an early event typically preceding fibrosis. The HA that accumulates in inflamed airways is of a high molecular weight (>1600 kDa) but can be broken down into smaller fragments (<150 kDa) by inflammatory and disease-related mechanisms that have profound effects on HA pathobiology. During inflammation in the airways, HA is often covalently modified with heavy chains from inter-alpha-inhibitor via the enzyme tumor-necrosis-factor-stimulated-gene-6 (TSG-6) and this modification promotes the interaction of leukocytes with HA matrices at sites of inflammation. The clearance of HA and its return to normal levels is essential for the proper resolution of inflammation. These data portray HA matrices as an important component of normal airway physiology and illustrate its integral roles during tissue injury and repair among a variety of respiratory diseases.

No MeSH data available.


Related in: MedlinePlus