Perl A. mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging. Ann N Y Acad Sci. 2015;1346:33–44.

CAS  PubMed  PubMed Central  Google Scholar 

Miller JL. Sirolimus approved with renal transplant indication. Am J Health Syst Pharm. 1999;56:2177–8.

PubMed  Google Scholar 

Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM, Schmithorst VJ, Laor T, Brody AS, Bean J, et al. Sirolimus for Angiomyolipoma in tuberous sclerosis complex or Lymphangioleiomyomatosis. N Engl J Med. 2008;358:140–51.

CAS  PubMed  PubMed Central  Google Scholar 

Luo Q, Chai X, Xin X, Ouyang W, Deng F. Maternal hyperglycemia inhibits pulmonary vasculogenesis during mouse fetal lung development by promoting gbetal Ubiquitination-dependent mammalian target of Rapamycin assembly. Diabetol Metab Syndr. 2023;15:49.

CAS  PubMed  PubMed Central  Google Scholar 

Zhang K, Yao E, Chuang E, Chen B, Chuang EY, Chuang PT. mTORC1 signaling facilitates differential stem cell differentiation to shape the developing murine lung and is associated with mitochondrial capacity. Nat Commun. 2022;13:7252.

CAS  PubMed  PubMed Central  Google Scholar 

Hafen E, Stocker H. How are the sizes of cells, organs, and bodies controlled? PLoS Biol. 2003;1:E86.

PubMed  PubMed Central  Google Scholar 

Conlon I, Raff M. Size control in animal development. Cell. 1999;96:235–44.

CAS  PubMed  Google Scholar 

Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;168:960–76.

CAS  PubMed  PubMed Central  Google Scholar 

Bulut-Karslioglu A, Biechele S, Jin H, Macrae TA, Hejna M, Gertsenstein M, Song JS, Ramalho-Santos M. Inhibition of mTOR induces a paused pluripotent state. Nature. 2016;540:119–23.

CAS  PubMed  PubMed Central  Google Scholar 

Bockaert J, Marin P. mTOR in brain physiology and pathologies. Physiol Rev. 2015;95:1157–87.

CAS  PubMed  Google Scholar 

Xu X-Y, Zhang Z, Su W-H, Zhang Y, Yu Y-Q, Li Y-X, Zong Z-H, Yu B-Z. Characterization of p70 S6 kinase 1 in early development of mouse embryos. Dev Dynamics: Official Publication Am Association Anatomists. 2009;238:3025–34.

CAS  Google Scholar 

Zhang Z, Zhang G, Xu X, Su W, Yu B. mTOR-rictor is the Ser473 kinase for AKT1 in mouse one-cell stage embryos. Mol Cell Biochem. 2012;361:249–57.

CAS  PubMed  Google Scholar 

Murakami M, Ichisaka T, Maeda M, Oshiro N, Hara K, Edenhofer F, Kiyama H, Yonezawa K, Yamanaka S. mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells. Mol Cell Biol. 2004;24:6710–8.

CAS  PubMed  PubMed Central  Google Scholar 

Goss K. Long-term pulmonary vascular consequences of perinatal insults. J Physiol. 2019;597:1175–84.

CAS  PubMed  Google Scholar 

Mohlin S, Hamidian A, von Stedingk K, Bridges E, Wigerup C, Bexell D, Pahlman S. PI3K-mTORC2 but not PI3K-mTORC1 regulates transcription of HIF2A/EPAS1 and vascularization in neuroblastoma. Cancer Res. 2015;75:4617–28.

CAS  PubMed  Google Scholar 

Ziegler ME, Hatch MM, Wu N, Muawad SA, Hughes CC. mTORC2 mediates CXCL12-induced angiogenesis. Angiogenesis. 2016;19:359–71.

CAS  PubMed  PubMed Central  Google Scholar 

Bellusci S, Grindley J, Emoto H, Itoh N, Hogan BL. Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung. Development. 1997;124:4867–78.

CAS  PubMed  Google Scholar 

Tang N, Marshall WF, McMahon M, Metzger RJ, Martin GR. Control of mitotic spindle angle by the RAS-regulated ERK1/2 pathway determines lung tube shape. Sci (New York NY). 2011;333:342–5.

CAS  Google Scholar 

Land SC. Hochachka’s hypoxia defense strategies and the development of the pathway for oxygen. Comp Biochem Physiol Part B Biochem Mol Biology. 2004;139:415–33.

Google Scholar 

van Tuyl M, Liu J, Wang J, Kuliszewski M, Tibboel D, Post M. Role of oxygen and vascular development in epithelial branching morphogenesis of the developing mouse lung. Am J Physiol Lung Cell Mol Physiol. 2005;288:L167–78.

PubMed  Google Scholar 

Depping R, Steinhoff A, Schindler SG, Friedrich B, Fagerlund R, Metzen E, Hartmann E, Köhler M. Nuclear translocation of hypoxia-inducible factors (HIFs): involvement of the classical importin alpha/beta pathway. Biochim Biophys Acta. 2008;1783:394–404.

CAS  PubMed  Google Scholar 

Bárdos JI, Ashcroft M. Negative and positive regulation of HIF-1: a complex network. Biochim Biophys Acta. 2005;1755:107–20.

PubMed  Google Scholar 

Düvel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL, Triantafellow E, Ma Q, Gorski R, Cleaver S, et al. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell. 2010;39:171–83.

PubMed  PubMed Central  Google Scholar 

Hudson CC, Liu M, Chiang GG, Otterness DM, Loomis DC, Kaper F, Giaccia AJ, Abraham RT. Regulation of Hypoxia-Inducible factor 1α expression and function by the mammalian target of Rapamycin. Mol Cell Biol. 2023;22:7004–14.

Google Scholar 

Scott CL, Walker DJ, Cwiklinski E, Tait C, Tee AR, Land SC. Control of HIF-1 and vascular signaling in fetal lung involves cross talk between mTORC1 and the FGF-10/FGFR2b/Spry2 airway branching periodicity clock. Am J Physiol Lung Cell Mol Physiol. 2010;299:L455–71.

CAS  PubMed  PubMed Central  Google Scholar 

Land SC, Tee AR. Hypoxia-inducible factor 1alpha is regulated by the mammalian target of Rapamycin (mTOR) via an mTOR signaling motif. J Biol Chem. 2007;282:20534–43.

CAS  PubMed  Google Scholar 

Olver RE, Walters DV, Wilson SM. Developmental regulation of lung liquid transport.Annu Rev Physiol 2004;66:77–101.

Mansley MK, Wilson SM. Effects of nominally selective inhibitors of the kinases PI3K, SGK1 and PKB on the insulin-dependent control of epithelial Na + absorption. Br J Pharmacol. 2010;161:571–88.

CAS  PubMed  PubMed Central  Google Scholar 

Xiang X, Yuan F, Zhao J, Li Z, Wang X, Guan Y, Tang C, Sun G, Li Y, Zhang W. Deficiency in pulmonary surfactant proteins in mice with fatty acid binding protein 4-Cre-mediated knockout of the tuberous sclerosis complex 1 gene. Exp Physiol. 2013;98:830–41.

CAS  PubMed  Google Scholar 

Lee H, Fei Q, Streicher A, Zhang W, Isabelle C, Patel P, Lam HC, Arciniegas-Rubio A, Pinilla-Vera M, Amador-Munoz DP, et al. mTORC1 is a mechanosensor that regulates surfactant function and lung compliance during ventilator-induced lung injury. JCI Insight 2021;6(1):e144192.

Morishita H, Kanda Y, Kaizuka T, Chino H, Nakao K, Miki Y, Taketomi Y, Guan JL, Murakami M, Aiba A, Mizushima N. Autophagy is required for maturation of Surfactant-Containing lamellar bodies in the lung and swim bladder. Cell Rep. 2020;33:108477.

CAS  PubMed  PubMed Central  Google Scholar 

Zhang L, Zhao S, Yuan LJ, Wu HM, Jiang H, Zhao SM, Luo G, Xue XD. Autophagy regulates hyperoxia-induced intracellular accumulation of surfactant protein C in alveolar type II cells.Mol Cell Biochem 2015;408:181–9.

CAS  PubMed  Google Scholar 

Zhang L, Zhao S, Yuan L, Wu H, Jiang H, Luo G. Hyperoxia-mediated LC3B activation contributes to the impaired transdifferentiation of type II alveolar epithelial cells (AECIIs) to type I cells (AECIs). Clin Exp Pharmacol Physiol. 2016;43:834–43.

CAS  PubMed  Google Scholar 

Zhang D, Wu L, Du Y, Zhu Y, Pan B, Xue X, Fu J. Autophagy inducers restore impaired autophagy, reduce apoptosis, and attenuate blunted alveolarization in hyperoxia-exposed newborn rats. Pediatr Pulmonol. 2018;53:1053–66.

PubMed  Google Scholar 

Sureshbabu A, Syed M, Das P, Janér C, Pryhuber G, Rahman A, Andersson S, Homer RJ, Bhandari V. Inhibition of Regulatory-Associated protein of mechanistic target of Rapamycin prevents Hyperoxia-Induced lung injury by enhancing autophagy and reducing apoptosis in neonatal mice. Am J Respir Cell Mol Biol. 2016;55:722–35.

CAS  PubMed  PubMed Central  Google Scholar 

Zhang L, Soni S, Hekimoglu E, Berkelhamer S, Cataltepe S. Impaired autophagic activity contributes to the pathogenesis of bronchopulmonary dysplasia. Evidence from murine and baboon models. Am J Respir Cell Mol Biol. 2020;63:338–48.

CAS  PubMed  PubMed Central  Google Scholar 

Tigani B, Hannon JP, Schaeublin E, Mazzoni L, Fozard JR. Effects of immunomodulators on airways hyperresponsiveness to adenosine induced in actively sensitised brown Norway rats by exposure to allergen. Naunyn Schmiedebergs Arch Pharmacol. 2003;368:17–25.

CAS  PubMed  Google Scholar 

Gao W, Cai L, Xu X, Fan J, Xue X, Yan X, Qu Q, Wang X, Zhang C, Wu G. Anti-CTGF single-chain variable fragment dimers inhibit human airway smooth muscle (ASM) cell proliferation by down-regulating p-Akt and p-mTOR levels. PLoS ONE. 2014;9:e113980.

PubMed