{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T15:07:42Z","timestamp":1769267262491,"version":"3.49.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A cardinal feature of asthma is airway hyperresponsiveness (AHR) to spasmogens, many of which activate G protein\u2013coupled receptors (GPCRs) on airway smooth muscle (ASM) cells. Asthma subtypes associated with allergy are characterized by eosinophilic inflammation in the lung due to the type 2 immune response to allergens and proinflammatory mediators that promote AHR. The degree to which intrinsic abnormalities of ASM contribute to this phenotype remains unknown. The regulators of G protein signaling (RGS) proteins are a large group of intracellular proteins that inhibit GPCR signaling pathways. RGS2- and RGS5-deficient mice develop AHR spontaneously. Although RGS4 is upregulated in ASM from patients with severe asthma, the effects of increased RGS4 expression on AHR in vivo are unknown. Here, we examined the impact of forced RGS4 overexpression in lung on AHR using transgenic (Tg) mice. Tg RGS4 was expressed in bronchial epithelium and ASM in vivo, and protein expression in lung was increased at least 4-fold in Tg mice compared with wild-type (WT) mice. Lung slices from Tg mice contracted less in response to the m3 muscarinic receptor agonist methacholine compared with the WT, although airway resistance in live, unchallenged mice of both strains was similar. Tg mice were partially protected against AHR induced by fungal allergen challenge due to weakened contraction signaling in ASM and reduced type 2 cytokine (IL-5 and IL-13) levels in Tg mice compared with the WT. These results provide support for the hypothesis that increasing RGS4 expression and\/or function could be a viable therapeutic strategy for asthma.<\/jats:p>","DOI":"10.1165\/rcmb.2017-0109oc","type":"journal-article","created":{"date-parts":[[2017,8,30]],"date-time":"2017-08-30T16:20:49Z","timestamp":1504110049000},"page":"89-98","source":"Crossref","is-referenced-by-count":18,"title":["RGS4 Overexpression in Lung Attenuates Airway Hyperresponsiveness in Mice"],"prefix":"10.1093","volume":"58","author":[{"given":"Laura A.","family":"Madigan","sequence":"first","affiliation":[{"name":"Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon S.","family":"Wong","sequence":"additional","affiliation":[{"name":"Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Laboratory of Asthma and Lung Inflammation, Cardiovascular and Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nariman","family":"Balenga","sequence":"additional","affiliation":[{"name":"Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia 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