{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T05:51:15Z","timestamp":1783749075526,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,12,7]],"date-time":"2012-12-07T00:00:00Z","timestamp":1354838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>New findings<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p><jats:p>Does tuberous sclerosis complex 1\u2013mammalian target of rapamycin (mTOR) signalling regulate the synthesis of surfactant proteins A and B and, if so, can this contribute to the postnatal death of <jats:italic>Fabp4\u2010Tsc1<\/jats:italic>cKO mice?<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p><jats:p>Our study reveals a novel mechanism for the regulation of alveolar surfactant proteins. Tuberous sclerosis complex 1\u2013mTOR signalling contributes to the regulation of synthesis of surfactant proteins A and B. Deficiency of tuberous sclerosis complex 1 in alveolar epithelial cells may contribute to the postnatal death of <jats:italic>Fabp4\u2010Tsc1<\/jats:italic>cKO mice.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>Tuberous sclerosis complex 1 (TSC1) forms a heterodimmer with tuberous sclerosis complex 2, to inhibit signalling by the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). The mTORC1 stimulates cell growth by promoting anabolic cellular processes, such as gene transcription and protein translation, in response to growth factors and nutrient signals. Originally designed to test the role of TSC1 in adipocyte function, mice in which the gene for TSC1 was specifically deleted by the fatty acid binding protein 4 (FABP4)\u2010<jats:italic>Cre<\/jats:italic> (<jats:italic>Fabp4\u2010Tsc1<\/jats:italic>cKO mice) died prematurely within 48 h after birth. The <jats:italic>Fabp4\u2010Tsc1<\/jats:italic>cKO mouse revealed a much smaller phenotype relative to the wild\u2010type littermates. Maternal administration of rapamycin, a classical mTOR inhibitor, significantly increased the survival time of <jats:italic>Fabp4\u2010Tsc1<\/jats:italic>cKO mice for up to 23 days. Both macroscopic and microscopic haemorrhages were observed in the lungs of <jats:italic>Fabp4\u2010Tsc1<\/jats:italic>cKO mice, while other tissues showed no significant changes. Levels of surfactant proteins A and B demonstrated a significant decrease in the <jats:italic>Fabp4\u2010Tsc1<\/jats:italic>cKO mice, which was rescued by maternal injection of rapamycin. Co\u2010localization of FABP4 or TSC1 with surfactant protein B was also detected in neonatal pulmonary tissues. Our study suggests that TSC1\u2013mTORC1 may be critical for the synthesis of surfactant proteins A and B.<\/jats:p>","DOI":"10.1113\/expphysiol.2012.069674","type":"journal-article","created":{"date-parts":[[2012,11,10]],"date-time":"2012-11-10T05:22:22Z","timestamp":1352524942000},"page":"830-841","source":"Crossref","is-referenced-by-count":11,"title":["Deficiency in pulmonary surfactant proteins in mice with fatty acid binding protein 4\u2010<i>Cre<\/i>\u2010mediated knockout of the tuberous sclerosis complex 1 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