{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:50:56Z","timestamp":1790661056524,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pterygium is one of the most common ocular surface diseases. During the initiation of pterygium, resting epithelial cells are activated and exhibit aberrant apoptosis and cell proliferation. Mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth, cell proliferation, protein synthesis, autophagy and transcription. However, the effect of mTORC1 activation in epithelial cells on pterygium development has not yet been reported. Additionally, the roles of mTORC1 in aberrant apoptosis and cell proliferation during the initiation of pterygium, and the underlying mechanisms, are not known. Herein, we evaluated mTOR signalling in pterygium growth and development. The results revealed that mTOR signalling, especially mTORC1 signaling, is highly activated, and aberrant apoptosis and cell proliferation were observed in pterygium. mTORC1 activation inhibits apoptosis in pterygium by regulating Beclin 1-dependent autophagy via targeting Bcl-2. mTORC1 also negatively regulates fibroblast growth factor receptor 3 (FGFR3) through inhibition of p73, thereby stimulating cell proliferation in pterygium. These data demonstrate that mTORC1 signalling is highly activated in pterygium and provide new insights into the pathogenesis and progression of pterygium. Hence, mTORC1 may be a novel therapeutic target for the treatment of pterygium.<\/jats:p>","DOI":"10.1038\/s41598-017-07844-y","type":"journal-article","created":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T14:18:38Z","timestamp":1501510718000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["mTORC1 regulates apoptosis and cell proliferation in pterygium via targeting autophagy and FGFR3"],"prefix":"10.1038","volume":"7","author":[{"given":"Yanli","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanchun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixia","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,4]]},"reference":[{"key":"7844_CR1","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1136\/bjo.77.11.734","volume":"77","author":"MT Coroneo","year":"1993","unstructured":"Coroneo, M. T. Pterygium as an early indicator of ultraviolet insolation: a hypothesis. Br J Ophthalmol \n                           77, 734\u2013739 (1993).","journal-title":"Br J Ophthalmol"},{"key":"7844_CR2","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.exer.2016.10.006","volume":"153","author":"A Hou","year":"2016","unstructured":"Hou, A., Law, K. P., Tin, M. Q., Lim, Y. P. & Tong, L. In vitro secretomics study of pterygium-derived fibroblasts by iTRAQ-based quantitative proteomics strategy. Experimental eye research \n                           153, 14\u201322, doi:10.1016\/j.exer.2016.10.006 (2016).","journal-title":"Experimental eye research"},{"key":"7844_CR3","first-page":"1687","volume":"17","author":"K Liang","year":"2011","unstructured":"Liang, K. et al. Expression of cell proliferation and apoptosis biomarkers in pterygia and normal conjunctiva. Molecular vision \n                           17, 1687\u20131693 (2011).","journal-title":"Molecular vision"},{"key":"7844_CR4","doi-asserted-by":"publisher","first-page":"3723","DOI":"10.1167\/iovs.16-19402","volume":"57","author":"YH Cui","year":"2016","unstructured":"Cui, Y. H. et al. Regulation of Apoptosis by miR-122 in Pterygium via Targeting Bcl-w. Investigative ophthalmology & visual science \n                           57, 3723\u20133730, doi:10.1167\/iovs.16-19402 (2016).","journal-title":"Investigative ophthalmology & visual science"},{"key":"7844_CR5","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1126\/science.1147379","volume":"318","author":"X Bai","year":"2007","unstructured":"Bai, X. et al. Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38. Science \n                           318, 977\u2013980, doi:10.1126\/science.1147379 (2007).","journal-title":"Science"},{"key":"7844_CR6","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.cellsig.2016.02.008","volume":"28","author":"BB Bridgeman","year":"2016","unstructured":"Bridgeman, B. B. et al. Inhibition of mTOR by apigenin in UVB-irradiated keratinocytes: A new implication of skin cancer prevention. Cellular signalling \n                           28, 460\u2013468, doi:10.1016\/j.cellsig.2016.02.008 (2016).","journal-title":"Cellular signalling"},{"key":"7844_CR7","doi-asserted-by":"publisher","first-page":"4452","DOI":"10.1167\/iovs.13-11684","volume":"54","author":"YJ Shin","year":"2013","unstructured":"Shin, Y. J. et al. Chemical injury-induced corneal opacity and neovascularization reduced by rapamycin via TGF-beta1\/ERK pathways regulation. Investigative ophthalmology & visual science \n                           54, 4452\u20134458, doi:10.1167\/iovs.13-11684 (2013).","journal-title":"Investigative ophthalmology & visual science"},{"key":"7844_CR8","doi-asserted-by":"publisher","first-page":"e12","DOI":"10.1111\/aos.12237","volume":"92","author":"J Zhu","year":"2014","unstructured":"Zhu, J. et al. Systemic application of sphingosine 1-phosphate receptor 1 immunomodulator inhibits corneal allograft rejection in mice. Acta ophthalmologica \n                           92, e12\u201321, doi:10.1111\/aos.12237 (2014).","journal-title":"Acta ophthalmologica"},{"key":"7844_CR9","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1007\/s00417-013-2435-z","volume":"251","author":"Q Meng","year":"2013","unstructured":"Meng, Q. et al. mTOR regulates TGF-beta(2)-induced epithelial-mesenchymal transition in cultured human lens epithelial cells. Graefe\u2019s archive for clinical and experimental ophthalmology=Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie \n                           251, 2363\u20132370, doi:10.1007\/s00417-013-2435-z (2013).","journal-title":"Graefe\u2019s archive for clinical and experimental ophthalmology=Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie"},{"key":"7844_CR10","first-page":"1646","volume":"16","author":"H Liu","year":"2010","unstructured":"Liu, H. et al. The effects of rapamycin on lens epithelial cell proliferation, migration, and matrix formation: an in vitro study. Molecular vision \n                           16, 1646\u20131653 (2010).","journal-title":"Molecular vision"},{"key":"7844_CR11","doi-asserted-by":"publisher","first-page":"13833","DOI":"10.3390\/ijms150813833","volume":"15","author":"F Tian","year":"2014","unstructured":"Tian, F. et al. Rapamycin-Induced apoptosis in HGF-stimulated lens epithelial cells by AKT\/mTOR, ERK and JAK2\/STAT3 pathways. International journal of molecular sciences \n                           15, 13833\u201313848, doi:10.3390\/ijms150813833 (2014).","journal-title":"International journal of molecular sciences"},{"key":"7844_CR12","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.3892\/mmr.2015.4645","volume":"13","author":"R Guo","year":"2016","unstructured":"Guo, R. et al. TGF-beta2 induces epithelial-mesenchymal transition in cultured human lens epithelial cells through activation of the PI3K\/Akt\/mTOR signaling pathway. Molecular medicine reports \n                           13, 1105\u20131110, doi:10.3892\/mmr.2015.4645 (2016).","journal-title":"Molecular medicine reports"},{"key":"7844_CR13","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1126\/science.290.5497.1717","volume":"290","author":"DJ Klionsky","year":"2000","unstructured":"Klionsky, D. J. & Emr, S. D. Autophagy as a regulated pathway of cellular degradation. Science \n                           290, 1717\u20131721 (2000).","journal-title":"Science"},{"key":"7844_CR14","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.semnephrol.2016.03.005","volume":"36","author":"A Havasi","year":"2016","unstructured":"Havasi, A. & Dong, Z. Autophagy and Tubular Cell Death in the Kidney. Seminars in nephrology \n                           36, 174\u2013188, doi:10.1016\/j.semnephrol.2016.03.005 (2016).","journal-title":"Seminars in nephrology"},{"key":"7844_CR15","doi-asserted-by":"publisher","unstructured":"Hu, Y. et al. Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury. 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Autophagy \n                           5, 114\u2013116 (2009).","journal-title":"Autophagy"},{"key":"7844_CR18","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.bbrc.2010.03.084","volume":"394","author":"AE Sayan","year":"2010","unstructured":"Sayan, A. E. et al. p73 and p63 regulate the expression of fibroblast growth factor receptor 3. Biochemical and biophysical research communications \n                           394, 824\u2013828, doi:10.1016\/j.bbrc.2010.03.084 (2010).","journal-title":"Biochemical and biophysical research communications"},{"key":"7844_CR19","doi-asserted-by":"publisher","first-page":"12297","DOI":"10.1074\/jbc.M900573200","volume":"284","author":"IG Ganley","year":"2009","unstructured":"Ganley, I. G. et al. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. The Journal of biological chemistry \n                           284, 12297\u201312305, doi:10.1074\/jbc.M900573200 (2009).","journal-title":"The Journal of biological chemistry"},{"key":"7844_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.11.016","author":"Z Akyol","year":"2016","unstructured":"Akyol, Z., Coker-Gurkan, A., Arisan, E. D., Obakan-Yerlikaya, P. & Palavan-Unsal, N. DENSpm overcame Bcl-2 mediated resistance against Paclitaxel treatment in MCF-7 breast cancer cells via activating polyamine catabolic machinery. Biomedicine & pharmacotherapy=Biomedecine & pharmacotherapie. doi:10.1016\/j.biopha.2016.11.016 (2016).","journal-title":"Biomedicine & pharmacotherapy=Biomedecine & pharmacotherapie"},{"key":"7844_CR21","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.cell.2005.07.002","volume":"122","author":"S Pattingre","year":"2005","unstructured":"Pattingre, S. et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. 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