Short Communication - Journal of Pulmonology and Clinical Research (2021) Volume 4, Issue 6
Smooth muscle proliferation is stimulated by the airway epithelium
We hypothesized that an injured airway epithelium secretes soluble mediators at biologically relevant concentrations to stimulate smooth muscle cell hyperplasia. To address this hypothesis, we used a co-culture model of primary Normal Bronchial Epithelial Cells (NHBE) and primary normal Human Airway Smooth Muscle cells (HASM), as well as an in vivo model of epithelial injury in the rabbit trachea. Our results demonstrate that an injured airway epithelium promotes HASM cell proliferation. Furthermore, proliferation in the smooth muscle (trachealis) region was observed in the rabbit trachea after repeated epithelial injury. To our knowledge, this is the first report demonstrating the role of the epithelium in airway smooth muscle cell proliferation. The results are consistent with an increasing interest in epithelial dysfunction as a target of therapeutic intervention in airway diseases. Discussion Tissue injury along with inflammation is associated with remodeling as observed in several airway diseases including asthma, chronic obstructive pulmonary disease, and fibrosing alveolitis. One feature of airway remodeling is smooth muscle cell hyperplasia, which impacts airway caliber and decreases lung function. Current anti-inflammatory strategies do not reverse smooth muscle hyperplasia, creating a need for alternative therapies. Using both a novel in vitro co-culture model as well as an in vivo model of epithelial injury in the trachea, our study demonstrates that epithelial-derived mediators stimulate airway smooth muscle proliferation at baseline and after injury. We identified IL-6, IL-8, and MCP-1 as mediators, which contribute significantly to proliferation after injury, and MMP-9 as a novel mediator involved in both baseline and injury-induced proliferation. IL-6, IL-8, and MMP-9 levels are affected by the co-culture of NHBE and HASM, while MCP-1 is mainly produced by HASM. While not all diseases with epithelial injury manifest airway smooth muscle proliferation, our results provide potentially new targets to limit smooth muscle hyperplasia in the airways, and are consistent with a growing interest in the health of the airway epithelium.