289:
Airway epithelial cells enhances tissue plasminogen activator by short chain fatty acids via G protein coupled receptor 41 and 43
Saturday, March 3, 2018: 2:30 PM
S330GH (Convention Center)
Yoshimasa Imoto, MD PhD, , , , , , , , , , , , , , , , , ,
RATIONALE: Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease generally divided based on presence or absence of nasal polyps (NPs). Excessive fibrin deposition is one of the features of NPs. Tissue plasminogen activator is expressed in epithelial cells and initiates fibrin degradation, however, t-PA expression is reduced in NPs. Identifying compounds that can induce expression of t-PA would be a potential new strategy for the treatment of NPs. We hypothesized that short chain fatty acids (SCFAs) can induce t-PA in airway epithelial cells via their receptors, G protein coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3) and GPR43/FFAR2.

METHODS: We performed immunohistochemistry (IHC) to reveal whether GPR41 and GPR43 are present in nasal tissue. To test induction of t-PA, primary normal human bronchial epithelial (NHBE) cells were stimulated with SCFAs. Mediation of responses by SCFA receptors was evaluated by specific receptor gene silencing with siRNA.

RESULTS: IHC study revealed that airway epithelial cells expressed both GPR41 and GPR43 in vitro and in vivo. Propionic acid, butyric acid, and valeric acid strongly induced expression of t-PA mRNA and protein (range X fold to Y fold, p<.05) in NHBE cells. T-PA released into the supernatant was shown to be in the active form. The induction of t-PA by SCFAs was dependent upon both GPR41 and GPR43.

CONCLUSIONS: SCFAs were shown to induce airway epithelial cell expression of t-PA via GPR41 and GPR43. Potent compounds that activate these receptors in vivo may have value by reducing fibrin deposition and shrinking nasal polyps.