Related Experiment Videos
Low molecular weight hyaluronan from stretched lung enhances interleukin-8 expression
Marcella M Mascarenhas1, Regina M Day, Cristiaan D Ochoa
1Pulmonary and Critical Care Unit, Massachusetts General Hospital, 55 Fruit Street, Bulfinch-148, Boston, MA 02114, USA. mmascarenhas@partners.org
Summary
Mechanical ventilation can cause lung injury. Low molecular weight hyaluronan (LMW HA) produced by HAS 3 in lung fibroblasts contributes to this injury via cytokine release.
Area of Science:
- Biomedical Engineering
- Pulmonary Medicine
- Cell Biology
Background:
- Mechanical ventilation can lead to ventilator-induced lung injury (VILI) through lung overstretching.
- Low molecular weight hyaluronan (LMW HA) is known to induce cytokine production.
- Hyaluronan synthase 3 (HAS 3) is responsible for producing LMW HA.
Purpose of the Study:
- To investigate the role of HAS 3 in VILI.
- To determine if stretch-induced LMW HA production is dependent on HAS 3 mRNA expression.
- To explore the signaling pathways involved in stretch-induced LMW HA production.
Main Methods:
- Utilized an in vitro lung cell stretch model.
- Measured HAS 3 mRNA expression and LMW HA accumulation.
- Employed inhibitors of HAS 3, protein tyrosine kinases, and janus kinase 2.
- Assessed interleukin-8 production in epithelial cells.
Main Results:
- Cell stretch upregulated HAS 3 mRNA expression and induced LMW HA production in fibroblasts.
- Inhibitors blocked stretch-induced HAS 3 expression and LMW HA synthesis.
- Stretch-induced LMW HA significantly increased interleukin-8 production in epithelial cells.
Conclusions:
- De novo synthesis of LMW HA in lung fibroblasts is induced by mechanical stretch via tyrosine kinase signaling pathways.
- LMW HA may play a role in augmenting pro-inflammatory cytokine induction in VILI.
- Targeting HAS 3 or associated signaling pathways could be a therapeutic strategy for VILI.