{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T16:27:00Z","timestamp":1775233620252,"version":"3.50.1"},"reference-count":50,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2012,10,15]]},"abstract":"<jats:p> Our laboratory has previously reported that bronchial epithelial cells (BEC) express a regulatory cascade of classic neurotransmitters and receptors that communicate in an almost neuronal-like manner to achieve physiological regulation. In this paper we show that the similarity between neurotransmitter signaling in neurons and BEC extends to the level of transmitter receptor allosteric modulators. Lynx1 is a member of the ly-6\/three-finger superfamily of proteins, many of which modulate receptor signaling activity. Lynx1 specifically has been shown to modulate nicotinic acetylcholine receptor (nAChR) function in neurons by altering receptor sensitivity and desensitization. We now report that lynx1 forms a complex with \u03b17 nAChR in BEC and serves to negatively regulate \u03b17 downstream signaling events. Treatment of primary cultures of BEC with nicotine increased levels of nAChR subunits and that increase was potentiated by lynx1 knockdown. Lynx1 knockdown also potentiated the nicotine-induced increase in GABA<jats:sub>A<\/jats:sub> receptors (GABA<jats:sub>A<\/jats:sub>R) and MUC5AC mRNA expression, and that effect was blocked by \u03b17 antagonists and \u03b17 knockdown. In parallel with the increases in nAChR, GABA<jats:sub>A<\/jats:sub>R, and mucin mRNA levels, lynx1 knockdown also increased levels of p-Src. Consistent with this, inhibition of Src signaling blocked the ability of the lynx1 knockdown to increase basal and nicotine-stimulated GABA<jats:sub>A<\/jats:sub>R and mucin mRNA expression. Thus lynx1 appears to act as a negative modulator of \u03b17 nAChR-induced events by inhibiting Src activation. This suggests that lynx1 agonists or mimetics are a potentially important therapeutic target to develop new therapies for smoking-related diseases characterized by increased mucin expression. <\/jats:p>","DOI":"10.1152\/ajplung.00075.2012","type":"journal-article","created":{"date-parts":[[2012,8,24]],"date-time":"2012-08-24T23:46:30Z","timestamp":1345851990000},"page":"L661-L668","source":"Crossref","is-referenced-by-count":19,"title":["The ly-6 protein, lynx1, is an endogenous inhibitor of nicotinic signaling in airway epithelium"],"prefix":"10.1152","volume":"303","author":[{"given":"Xiao Wen","family":"Fu","sequence":"first","affiliation":[{"name":"Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen S.","family":"Rekow","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Oregon National Primate Research Center, Oregon 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