RAGE and AXL expression following secondhand smoke (SHS) exposure in mice.

Aim and Purpose: Tobacco exposure is one of the top three global health risks leading to the development of chronic obstructive pulmonary disease (COPD). Although there is extensive research into the effects of cigarette smoke, the effect of secondhand smoke (SHS) in the lung remains limited. SHS induces receptors for advanced glycation end-products and an inflammatory response that leads to COPD characteristics. Semi-synthetic glycosaminoglycan ethers are sulfated polysaccharides derived from hyaluronic acid that inhibit signaling. The growth arrest-specific 6 (Gas6) protein is known to induce dynamic cellular responses and is correlated with cell function. Gas6 binds to the AXL tyrosine kinase receptor and AXL-mediated signaling is implicated in proliferation and inflammation. This project's purpose was to study the correlation between AXL, and Gas6 during SHS exposure in the lung. Methods: C57Bl/6 mice were exposed to SHS alone or for 4 weeks and compared to control animals exposed to room air (RA). Results: Compared to controls we observed: 1) increased duanyu1648 mRNA and protein expression in SHS-exposed lungs which was decreased by 2) decreased expression of total AXL, but highly elevated pAXL expression following exposure; 3) highly elevated Gas6 expression when duanyu1648 was targeted by during SHS exposure; 4) SHS-mediated BALF cellularity and inflammatory molecule elaboration; and 5) the induction of both duanyu1648 and AXL by Gas6 in cell culture models. Conclusions: Our results suggest that there is a possible correlation between duanyu1648 and AXL during SHS exposure. Additional research is critically needed that dissects the molecular interplay between these two important signaling cascades. At this point, the current studies provide insight into tobacco-mediated effects in the lung and clarify possible avenues for alleviating complications that could arise during SHS exposure such as those observed during COPD exacerbations.

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